SlideShare ist ein Scribd-Unternehmen logo
1 von 36
Downloaden Sie, um offline zu lesen
Report of the First National Anti TB Drug Resistance Survey India
Report of the First National Anti TB Drug Resistance Survey India
Report of the First National Anti TB Drug Resistance Survey India
Report of the First National Anti TB Drug Resistance Survey India
Report of the First National Anti TB Drug Resistance Survey India
Report of the First National Anti TB Drug Resistance Survey India
i
List of contributors
Survey team
Principal investigators: Dr Jagdish Prasad, Director General Health Services, Dte GHS,
MoHFW; Dr Prahlad Kumar, National Tuberculosis Institute, Bangalore, Dte GHS, MoHFW
Co-principal investigator: Dr Ranjani Ramachandran, WHO Country Office for India
Team members who contributed to the survey
Protocol development: Dr S. Anand, Dr Malik Parmar, Dr Kiran Rade, Dr Puneet Dewan, Dr
Patrick Moonan
Laboratory services: Dr R. Lakshmi, Dr S. Lakshmi and the team of technologists at NTI
Data collection and software: Mr Jitendra Suryavamshi
Quality assurance for laboratory: National Institute for Research in Tuberculosis, Chennai
and SRL Antwerp, Belgium
Data analysis and data quality management: Dr A.N. Sreenivas, Dr Malik Parmar, Dr Kiran
Rade, Dr Puneet Dewan, Mr Matteo Zignol, Mr C. Sismanidis
Programme support: DDG TB, ADDG TB, State TB Officers, District TB Officers and WHO-
RNTCP Technical Support Network
Report of the First National Anti TB Drug Resistance Survey India
ii
Abbreviations
CBNAAT cartridge-based nucleic acid amplification test
CIF clinical information form
DEFF design effect
DMC designated microscopy centre
DRS drug resistance survey
DR-TB drug-resistant TB
IQC internal quality control
M. tuberculosis Mycobacterium tuberculosis
MDR-TB multidrug-resistant TB
MGIT mycobacteria growth indicator tube
NDRS National Anti-tuberculosis Drug Resistance Survey
NIRT National Institute for Research in Tuberculosis
NTI National Tuberculosis Institute
PLHIV people living with human immunodeficiency virus
PMDT programmatic management of drug-resistant TB
QA quality assurance
RNTCP Revised National Tuberculosis Control Programme
RR-TB rifampicin-resistant TB
SRL Supranational Reference Laboratory
STLS senior TB laboratory supervisor
STS senior treatment supervisor
TB tuberculosis
TU TB unit
WHO World Health Organization
XDR-TB extensively drug-resistant TB
Report of the First National Anti TB Drug Resistance Survey India
1
Executive summary
India has more new tuberculosis (TB) patients annually than any other country globally,
contributing to 27% of the world’s TB burden. About 2.79 million TB patients are estimated
to be added annually. The Revised National Tuberculosis Control Programme (RNTCP)
notified around 1.94 million TB patients in 2016 (1).
As per the Global TB Report 2017 (1), worldwide approximately 4.1% of new TB patients and
19% of previously treated TB patients have multidrug resistant-TB (MDR-TB), i.e. TB
resistant to at least two of the first-line drugs – isoniazid and rifampicin. Extensively drug-
resistant TB (XDR-TB), defined as MDR-TB with additional resistance to at least one
fluoroquinolone and one second line injectable drug, has been reported by 123 countries.
The proportion of XDR-TB among MDR-TB patients is 6.2% worldwide. The estimated
number of MDR/rifampicin resistant (RR)-TB in India is 147 000, accounting for one fourth of
the global burden of MDR/RR-TB (1).
India initiated the programmatic management of drug resistant TB (PMDT) in 2007 to
address the emerging problem of drug resistant-TB (DR-TB), and the national PMDT scale-up
was achieved by March 2013. The treatment success rate among MDR-TB patients in India is
consistently about 46% and the death rate is around 20%, as against the global level of
treatment success rate of 52% and death rate of 17%. High rates of treatment failure and
deaths are associated with fluoroquinolone resistance in the Indian cohort of MDR-TB
patients (2).
India has sub-national data from state level anti-TB drug resistant surveys conducted in the
past (3); However the epidemiology of DR-TB in India has never been studied nationally.
Knowing the epidemiology of DR-TB is essential to guide development of evidence-based
strategies to combat DR-TB in India. In view of the above, the Government of India decided
to conduct a National Anti-TB Drug Resistance Survey (NDRS) to know the prevalence of
drug resistance among TB patients with particular focus on MDR-TB among both new and
previously treated TB patients.
This is the largest ever NDRS conducted by any country in the world and the first ever survey
having drug susceptibility testing (DST) for 13 anti-TB drugs using the automated liquid
culture system, mycobacteria growth indicator tube (MGIT) 960®.
A total of 5280 sputum smear-positive pulmonary TB patients (3240 new and 2040
previously treated) diagnosed at the designated microscopy centres (DMCs) of RNTCP were
enrolled in the survey.
2
The results of the survey showed that:
 MDR-TB is 6.19% (CI 5.54–6.90%) among all TB patients with 2.84% (CI 2.27–3.50%)
among new and 11.60% (CI 10.21–13.15%) among previously treated TB patients.
 Among MDR-TB patients, additional resistance to any fluoroquinolones was 21.82%
(17.33–26.87%), and 3.58% (1.8–6.32%) to any second-line injectable drugs.
 Among MDR-TB patients, additional resistance to at least one drug from each of the
two classes, i.e. fluoroquinolone and second-line injectable drugs (XDR-TB) was 1.3%
(0.36–3.30%).
 Any first- or second line drug resistance among all TB patients is 28.0% (CI 26.77–
29.29%) with 22.54% (CI 21.10–24.10%) among new and 36.82% (CI 34.64–39.04%)
among previously treated TB patients.
 Any isoniazid resistance is 11.06% (CI 9.97–12.22%) and 25.09% (CI 23.1–-27.11%)
among new and previously treated TB patients, respectively.
 Any pyrazinamide resistance is 6.95% (CI 6.07–7.91%) and 8.77% (7.53–10.13%)
among new and previously treated TB patients, respectively.
MDR-TB rates at the national level are still within the range of previous state-level surveys
conducted in India. However, more than a quarter of TB patients in India have drug
resistance to one or the other anti-TB drug. Fluoroquinolone resistance among MDR-TB
patients is high and is similar to resistance rates reported by the RNTCP. The survey results
clearly indicate that drug resistance is present in all settings, and the wide range of
resistance patterns from any isoniazid resistance to XDR-TB needs to be addressed with
strengthening of drug resistance surveillance, universal DST and appropriate DST guided
treatment strategies.
3
1. Introduction
1.1 Country profile
With a population of 1.32 billion, India has the highest burden of tuberculosis (TB) and drug-
resistant TB (DR-TB) in the world. The Global TB Report 2017 published by World Health
Organization (WHO) estimates that India contributes 27% (2.79 million) and 25% (147 000)
of the global burden of TB and multi-drug resistant TB (MDR-TB), respectively (1). The
Revised National Tuberculosis Control Programme (RNTCP) has notified 1.94 million patients
in 2016 (1). India has been locating and treating MDR-TB patients since 2007 and achieved
complete geographical coverage of programmatic management of drug-resistant TB (PMDT)
services in 2013.
Up till 2016, 1 413 331 TB patients have been tested for drug resistance and 139 369
MDR/rifampicin-resistant (RR)-TB cases had been detected in India. Among them, 126 136
MDR/RR-TB and 6377 extensively drug-resistant (XDR)-TB patients have been put on
treatment.
In 2016 alone, 580 438 TB patients have been tested, 37 358 MDR/RR-TB have been
diagnosed and 32 914 MDR/RR-TB and 2475 XDR-TB patients have been put on treatment in
India (1). These numbers would increase in years to come as India has initiated
implementation of the policy of universal drug-susceptibility testing (DST) in phases since
mid-2017.
1.2 Statement of the problem
There have been a number of reports in the past on drug resistance in India A majority of
them used non-standardized methodologies, biased samples, and were usually conducted at
tertiary-level care facilities. However, there is data generated through clinical trials
conducted in Tuberculosis Research Centre (now National Institute for Research in
Tuberculosis [NIRT]), Chennai where rates of RR-TB and MDR-TB are available from the early
1980s from continuous surveillance of rifampicin resistance. This has been slowly increasing
from 0% to 2% among new TB patients till date (Fig. 1). This graph shows the rates of drug
resistance including MDR-TB. MDR-TB has been increasing from less than 1% in the early
nineties to 2.0% in 2006. Since then, the rates of MDR-TB have been almost static. (Data
from 2007 onwards is not shown in Fig. 1).
4
Fig. 1: Trend of first-line anti-TB drug resistance from historical surveys
H – Isoniazid; S- Streptomycin; SH – Streptomycin + Isoniazid; HR – Isoniazid + Rifampicin
In addition, valid state-level information about the extent of drug resistance is also available
(Table 1). These drug resistance surveys (DRSs) were conducted in accordance with standard
international protocol. Specimens were collected from a population-based sample of
sputum smear-positive patients diagnosed at RNTCP designated microscopy centres (DMCs).
Most of the state level surveys conducted in India have also reported patients of XDR-TB.
State representative DRSs in Andhra Pradesh and Gujarat (3) showed 4–6% XDR-TB cases
among MDR-TB isolates, with a high prevalence of fluoroquinolone resistance ranging from
21% to 25%.
Table 1: Rates of MDR-TB – state level surveys
Surveys, year and population New patients
Previously
treated
patients
Tamil Nadu State, 1997–1998 (60 million) 3.4% 25.0%
Gujarat State, 2007–2008 (56 million) (3) 2.4% 17.4%
Maharashtra State, 2008 (108 million) 2.7% 14.0%
Undivided Andhra Pradesh State, 2009 (86 million) 1.8% 11.8%
Tamil Nadu State, 2011 (77 million) (unpublished) 1.8% 13.2%
Current knowledge on MDR-TB in India
During the initial phase of PMDT implementation, RNTCP offered DST to TB patients who
were at the highest risk for MDR-TB, such as treatment failures and contacts of MDR-TB. As
the diagnostic capacity increased, the offer of DST was expanded to cover TB patients with
moderate/lower risk of MDR-TB. RNTCP continued to expand its DST coverage over the
years to test most TB patients with upfront cartridge-based nucleic acid amplification test
(CBNAAT) (Xpert MTB/RIF) followed by baseline second line DST, and has embarked upon
phased implementation of universal DST since mid-2017.
0
2
4
6
8
10
12
14
16
18
56-57
57-58
61-
61-62
62-63
63-66
67-68
68-69
70-72
72-74
74-77
77-80
80-85
85-86
86-90
90-95
95-9898-20012001-032004-06
H
S
SH
HR
5
Apart from DST, CBNAAT is also offered for diagnosis of TB in key populations like people
living with human immunodeficiency virus (PLHIV), children, those with extra-pulmonary
signs/symptoms and smear negative patients with chest X-ray suggestive of TB, for
microbiological confirmation of TB.
The rates of MDR/RR-TB observed over the past decade in the programme as the DST offer
expanded from highest risk cases to those at least risk of MDR-TB are shown in Table 2.
Table 2: MDR/RR-TB reported by RNTCP (PMDT services)
Rationale
India is one of the highest burden countries for TB and MDR-TB. However, the epidemiology
of DR-TB in India has never been studied nationally. This is essential to measure the DR-TB
burden and to guide development of evidence-based strategies to combat DR-TB in India. In
view of the above, the Government of India decided to conduct a National Anti-Tuberculosis
Drug Resistance Survey (NDRS) to inform on the prevalence of drug resistance among TB
patients, with particular focus on MDR-TB among both new and previously treated TB
patients. Accordingly, the NDRS protocol was developed by National Tuberculosis Institute
(NTI) and WHO for the RNTCP.
1.3 Aim and objectives
Aim
The aim of the survey was to find out the proportion of MDR-TB patients among new and
previously treated TB patients diagnosed at RNTCP DMCs.
General objective
The general objective was to understand the epidemiology of DR-TB in the country to guide
national policy and strategies to prevent further emergence and to control the problem.
Rates of MDR/RR-TB reported under RNTCP –
India’s routine surveillance data
Among new TB
patients
Among previously
treated patients
2007–2012 (n = 144 326) NA 19%
2013–2015 (n = 779 300) 5% 11%
2016 (n = 580 438) 4% 9%
6
Specific objectives
Primary objectives
 To determine the prevalence of MDR-TB among newly diagnosed sputum smear-
positive TB patients;
 To determine the prevalence of MDR-TB among previously treated sputum
smear-positive TB patients.
Secondary objectives
 To determine the prevalence of second line anti-TB drug resistance in
Mycobacterium tuberculosis (M. tuberculosis) strains with confirmed resistance to
isoniazid and rifampicin;
 To describe drug resistance patterns of M. tuberculosis strains collected from
newly diagnosed sputum smear-positive TB patients;
 To describe drug resistance patterns of M. tuberculosis strains collected from
previously treated sputum smear-positive TB patients.
7
2. Materials and methods
2.1 Study design
This was a cross-sectional study among all new smear-positive TB patients and all previously
treated TB patients diagnosed in the RNTCP DMCs in India from August 2014 to July 2015.
2.2 Sample size determination
In 2012, RNTCP notified 1 467 585 total TB patients, of which 629 589 were new sputum
smear-positive TB patients, 317 616 were smear-negative TB patients, 234 029 were new
extra-pulmonary TB patients and 284 212 were previously treated TB patients of which
106 463 were relapse cases, 16 400 were treatment failures, 64 782 were TB patients who
were lost to follow up and 96 567 were other retreatment TB patients. This data was used
for arriving at the sample size for the survey.
The assumptions used to arrive at the sample size for new and previously treated patients to
be enrolled in the survey are depicted in Table 3.
Table 3: Assumptions made to calculate the sample size for new and previously treated
patients to be enrolled in the survey
Type of patient New Previously treated
Initial estimate of prevalence 0.03 0.15
Relative precision 34% 40%
Anticipated non-participation/loss rate 20%
Design effect (due to cluster sampling) 2.5
Previous state level studies have shown MDR-TB proportion among new and previously
treated TB patients as 3% and 15%, respectively. Using these as initial prevalence, the
sample size was obtained with a 34% relative precision in new TB patients and 40% relative
precision in previously treated TB patients. Based on the analysis of state level DRSs (DMCs
as sampling units) the design effect (DEFF) was reasonably fixed at 2.5, also accounting for
high levels of heterogeneity among the TB units (TUs). An anticipated non-participation or
loss rate was assumed to be 20%.
Thus, the sample size for new TB patients was derived as 3223 with a relative precision of
34%, i.e. (3% ± 1%) and a DEFF of 2.5 (with 20% loss included). For previously treated TB
8
patients with the proportion of MDR-TB at 15%, 40% relative precision, i.e. 17% ± 7% (10–
24% in previously treated overall) and DEFF of 2.5, the sample size was derived as 1991.
More number of TUs would have be better for analytical purposes but may not have been
practical. The fewer the number of respondents in each cluster, the lower the clustering
effect, which would increase sample variance, thus effectively reducing the estimating
power. Balancing both these factors, 120 TUs were chosen to account for analytic precision
and logistic implementation. As the programme was under the process of further
decentralization of TUs during the survey period, all the new TUs that fell under the original
120 TU clusters identified at baseline continued to contribute to the study.
Sampling strategy
The sampling strategy in this survey was a single-stage, weighted cluster sampling method,
in which clusters were selected with probability proportional to size, with each cluster
contributing a fixed number of new and previously treated TB patients. The cluster sampling
methodology is appropriate for India because of the logistical challenges and laboratory
capacity needed to cover all of the approximately over 14 000 DMCs in the country and
around 1.5 million TB patients notified each year.
The primary sampling unit in the survey was the RNTCP-defined TU and survey participants
were recruited from all DMCs in the selected TUs. Each TU represented a cluster. The
proportion of urban TUs in the selection was 24%.
The following methodology was used to select the TU clusters. A list of all TUs in the country
with the respective numbers of new sputum smear-positive TB patients, and previously
treated TB patients registered in the first quarter (January–March) of 2012 was compiled.
This data was annualized to calculate the estimated cumulative number of total TB patients.
TUs were selected using a weighted-cluster sample technique based on new sputum smear-
positive TB patients. Once TUs were selected, all DMCs in the selected TU would contribute
until the enrolment of cumulative number of expected patients reached the required
sample size. A total of 44 consecutive TB patients diagnosed at the DMCs from each
selected TU were recruited to include 27 new TB patients and 17 previously treated TB
patients per TU. Based on this, the total new and previously treated TB patients were
rounded off to 3280 and 2040.
Those patients who met the inclusion criteria but could not be included in the survey for
various reasons were replaced by consecutive patients diagnosed in the DMCs of the same
TU according to the sampling procedure described.
9
Inclusion criteria
a) Newly diagnosed sputum smear-positive pulmonary TB patients with no history of prior
treatment for TB, or a history of anti-TB treatment for less than 30 days. Enrolled
patients should not have been initiated in a course of anti-TB treatment.
b) Diagnosed patients with sputum smear-positive pulmonary TB with a history of previous
TB episode with more than 30 days of anti-TB treatment. This may include relapses,
treatment after default, treatment after failure, or other patients who have claimed to
have anti-TB treatment for more than 30 days. Enrolled patients should not have been
initiated in a course of anti-TB treatment for the current episode.
Exclusion criteria
a) Patients with sputum smear-negative pulmonary TB
b) Patients with exclusively extra pulmonary TB
c) Patients diagnosed at a correctional facility (i.e., jails, prisons, asylums)
d) Persons unwilling or unable to give informed consent.
There were no age restrictions, provided the patient fulfilled the above criteria.
2.3 Definitions
Anti-TB drug resistance among new TB patients: Newly diagnosed sputum smear-positive
pulmonary TB patients without a history of prior treatment for TB, or a history of treatment
for less than 30 days. Enrolled patients should not have been initiated in a course of anti-TB
treatment for the current episode.
Anti-TB drug resistance among previously treated TB patients: Diagnosed patients with
sputum smear-positive pulmonary TB with a history of prior anti-TB therapy. This may
include relapse, treatment after default and treatment after failure, or other patients who
have claimed to have anti-TB treatment for greater than 30 days. Enrolled patients should
not have been initiated in a course of anti-TB treatment for the current episode.
Multidrug resistant TB (MDR-TB): Patients with sputum smear-positive pulmonary TB with at
least one M. Tuberculosis isolate with demonstrated resistance to at least isoniazid and
rifampicin (with or without other first-line anti-TB drugs).
Extensively drug resistant TB (XDR-TB): Patients with sputum smear-positive pulmonary TB
with at least one M. Tuberculosis isolate with demonstrated resistance to isoniazid,
rifampicin, at least one fluoroquinolone (ofloxacin, levofloxacin or moxifloxacin), and at
least one injectable second line drug (amikacin, capreomycin or kanamycin).
10
2.4 Training and data collection
The data collection formats included the clinical information form (CIF) and the diary of
senior TB laboratory supervisors (STLS) for referral. A detailed CIF was designed for
collecting data on socio-demography, occupation, income, symptoms, duration of illness,
history of previous treatment, source of treatment, etc. The CIF was administered by the
medical officer at the TU level along with which an informed consent for participation in the
survey was also obtained from eligible patients.
Bar codes were applied to specimens, sputum containers, CIF and NDRS registers for
automated aligning of all survey related data collection of individual patients from all the
sites of survey.
A training video in English and local vernacular languages was developed for assisting the
state level trainers trained at a series of national training of trainers to provide cascade
training in the participating states, which gave a detailed account of all the survey
procedures for data collection. In addition, dedicated in-house software was developed by
NTI for real time data entry and validation.
2.5 Field activities
Consecutive sputum smear-positive TB patients diagnosed at each DMC of the selected TUs
were recruited according to the sampling methodology based on categorization (new or
previously treated). The senior treatment supervisor (STS) or STLS coordinated among the
DMCs of the respective TUs to ensure that patients were enrolled in chronological order for
the study. On identification of an eligible patient, he/she was given detailed information
about the survey and informed consent was obtained from each patient. Two additional
specimens were collected from the patient in falcon tubes (specimen C and D) and these
were transported in a bio-safe container under cool chain to NTI along with CIF. CIF was
filled in by the medical officer of the DMC and cross-checked by the STS or STLS to reconfirm
the categorization. CIFs of 10% of enrolled patients were re-validated by district-level staff
and another 10% by the RNTCP–WHO consultant as part of the data quality assurance
procedure. Recruitment continued until the numbers of patients in each category were
completed. Provider-initiated HIV counselling and testing was offered to all patients as per
RNTCP guidelines.
The target transit time for receiving the specimens at NTI was fixed not to exceed 72 h;
however, there was no rejection clause if received later than the target time. Attention was
paid to transport logistics in order to minimize transportation time, prevent leakage and
specimen contamination. Specimens were packed and transported as per RNTCP guidelines.
Only fresh sputum specimens were transported and processed.
11
For patients eligible to screen for MDR-TB, two more specimens (E and F) were also
collected for rapid molecular drug resistance testing as per the PMDT guidelines for routine
care and MDR/RR-TB patients detected were initiated on an appropriate DR-TB regimen.
DST results of the specimens processed under the NDRS were communicated by NTI to the
respective district and DR-TB centre for appropriate treatment initiation or modification.
2.6 Laboratory procedures
All specimens were handled in a negative-pressure environment as per the international
standards for biosafety and infection control for M. tuberculosis. Two sputum specimens
from each study patient were decontaminated using N-acetyl-L-cysteine–sodium citrate–
sodium-hydroxide (NALC-NaOH) procedure. Microscopy using auramine-O-phenol of the
concentrated deposit smear was performed and inoculated onto 7 ml MGIT tubes as per the
MGIT 960 System Manual (4) and RNTCP Laboratory manual (5). Back up cultures for both
specimens were maintained on LJ medium. One specimen was inoculated per tube. Tubes
identified as positive by the MGIT system were further identified as M. tuberculosis-complex
by using immune-chromatographic tests. DST was performed on only one positive-culture
after identification as M. tuberculosis using the modified proportion sensitivity method for
liquid culture system taking standard critical concentrations for isoniazid (0.1μg), rifampicin
(1.0μg), streptomycin (1.0μg), ethambutol (5.0μg) and pyrazinamide (100µg) (as per the
MGIT manual). For second line drugs, the drugs and concentrations as per the standard
critical concentrations, i.e. kanamycin (2.5μg), amikacin (1.0μg), capreomycin (2.5μg),
ofloxacin (2.0μg), levofloxacin (1.5μg), moxifloxacin (0.5µg), PAS (2.0µg) and ethionamide
(5.0µg) were used (6).
2.7 Quality assurance
Laboratory quality assurance (QA) (internal and external)
All laboratory procedures adhered to the internal quality control (IQC) procedures as per
RNTCP laboratory manual, and in accordance with international standards times (7). All data
relating to the survey and records pertaining to IQC were maintained in separate registers –
primary culture, identification and drug susceptibility testing, and IQC.
NTI participates in the regular annual proficiency panel exercise conducted by the Antwerp
WHO Coordinating Supranational Reference Laboratory (SRL). In addition, 10% of all isolates
were retested at NIRT (formerly TRC), also a WHO coordinating SRL for recording
reproducibility. The results of the annual proficiency testing with Antwerp were 100% for all
tested first- and second line drugs. The agreement for the drugs tested in the DRS as part of
reproducibility was also complete.
12
2.8 Data management
NDRS – Laboratory Information Management System (NDRS-LIMS)
With the historical experience with the manual systems used in past subnational DRS
surveys in India, NDRS was expected to offer several challenges in terms of logistics,
training, implementation, data management and analysis. Further, the task of monitoring a
survey of this magnitude for needful interventions and course corrections from NTI and
keeping the central, state and WHO monitoring committees abreast with the progress on
the field with periodic reports meant that the data collection and its reflection onto reports
had to be as real time as possible.
Hence, a customized web-based application was designed, developed and hosted at NTI to
cater to both the data collection and real time interaction with the 120 TUs for entering the
external quality assessment (EQA) results and also to facilitate the survey monitoring by
Central TB Division (CTD) and WHO. A state level survey monitoring committee was
established in every state and was also provided individual login to access relevant
information for real time monitoring of the survey. Apart from this, a customised survey
specific laboratory information management system was also developed and hosted to
facilitate a work flow integrated data capture mechanism. This ensured that real time
reporting was available for necessary interventions by the data monitoring committee at
NTI and in the states. Use of innovative tools like barcodes and optical mark recognition
(OMR) sheets for result capture ensured an error-free and efficient data management
process.
The applications were developed using open source software MySQL database and PHP
programming language. The hosting, periodic backup, data security measures
commensurate with the standards were deployed.
Customised unique specimen enrolment registers for each of the 120 TUs were designed
with unique barcodes for 5280 patients. The date and time of specimen collection were
recorded on these stickers and were affixed to the falcon specimen tubes before dispatch to
NTI. 10 560 sputum smear examinations, culture examinations by both liquid and solid
media and DSTs for all positive cultures had to be undertaken. In addition, Xpert MTB/RIF
(GeneXpert) testing for paediatric patients was undertaken. It was essential to design a data
management solution that was not only efficient, but also assisted the microbiologist to
track the survey progress in terms of specimens received, specimens whose result was
declared and specimens under process. Hence, a robust laboratory information
management system was designed to facilitate the work process flow. All the stages of
laboratory activities right from the specimen registration, specimen result declaration by lab
technician and result verification by the microbiologist were captured in real time by a LAN
based application. This brought in a decentralised yet effective mechanism of data
13
collection from the respective laboratory work benches, giving the supervisors an overview
of the operations in real time. Also, pre-printed lab stationary was deployed. Only specimen
and test specific result sheets were dynamically generated at the time of specimen
registration with the unique barcodes printed. Thus, human errors in declaration of results
to the wrong specimens were avoided as the process started by scanning of the barcodes.
Also, the results were declared on optical mark recognition (OMR) sheets which were
subsequently scanned and re-checked for any mismatch. These processes ensured a high
degree of quality and accuracy in declaration of the laboratory results.
Multilingual video e-tutors on the standard operating procedures were prepared and used
for training and as ready reference for all the survey personnel using the web portal.
Data analysis
The data was analysed.0 and Stata ver 12 statistical packages.
To ensure accuracy, double-data entry using SPSS ver 17was employed. Periodic data
verification and validation exercises was conducted to ensure data accuracy
To calculate the prevalence of anti-tuberculosis drug resistance, the denominator was taken
to be the number of patients with valid drug susceptibility results. However, it is also
important to report the number of results missing as a result, for example, of
contamination, or negative cultures.
A table comparing the number of patients enrolled from each diagnostic centre with the
expected number of expected based on the sampling method was prepared. These were
used to monitor enrolment and track specimens.
A table describing the proportion of patients with resistance to individual TB drugs, and to
different combinations of TB drugs, among new and previously treated patients was
prepared.
Proportion in age, sex, HIV status, type of re-treatment, source of previous treatment was
stratified by categories of resistance.
Data was stored in the dedicated system with password protection and only accessible to
authorized personnel. Backup data was also stored in a separate site and server for use in
case of any fault in the primary PC.
Ethical issues and approval
Approval of the Institutional Ethics Committee of NTI was obtained. Informed consent was
obtained from all patients enrolled for the study. The DST results of all patients were
14
communicated to the respective health facilities for standard of TB care as per national
guidelines.
2.9 Limitations
The study did not include patients managed in the private sector who do not come in
contact with the public health sector during the course of their disease, as getting an
appropriate specimen from such patients was beyond the scope of the study.
The survey was powered only for national prevalence of MDR-TB and not for state level
prevalence.
15
3 Results, discussion and conclusion
3.1 Survey quality
The survey commenced in July 2014 and 95% of the enrolments were completed by July
2015. However, the rest of the 5% took longer and were completed only by May 2016. This
longer intake period was significantly contributed to by paucity of previously treated TB
patients diagnosed in certain DMCs, though they had such patients during the period of
sample size determination period in 2012. After the initial conduct of three rounds of
training of trainers, the survey commenced as per the agreed staggered timeline, with TUs
which required 12 months or more starting to contribute to survey intake and those that
could contribute within 15–30 days being at the tail end of the survey period. However,
during the survey, intake was initially slow due to various reasons including some logistic
issues contributing to delay in intake. This was compensated during the last quarter of the
survey period (Fig. 2).
Fig. 2: Sample registration during the survey period
PT – Previously treated
Patients were enrolled from 120 TUs across the country. Of the 572 total DMCs within these
120 TUs, 530 DMCs participated in screening of patients to identify those eligible, while 524
(91.61%) DMCs contributed to survey samples.
Two specimens, A and B, were collected for routine management as per standard of care
articulated in the RNTCP. After obtaining an informed consent, eligible patients were
requested to provide two additional specimens (C and D) each from 5280 eligible patients.
These were collected and transported to NTI Bangalore along with the completely filled
CIFs, barcoded as per survey protocol. The specimens were from 3240 new TB patients and
0
200
400
600
800
1000
1200
1400
Jul-14
Sep-14
Nov-14
Jan-15
Mar-15
May-15
Jul-15
Sep-15
Nov-15
Jan-16
Mar-16
May-16
All
New
PT
95%
16
2040 patients previously treated for TB. A total of 212 specimens were rejected due to
various reasons and additional patients were enrolled as replacement.
The quality of both specimens was good for 98% of those collected with a minimal
percentage of leakage or less than 2 ml volume observed in 1.0% each as shown in Table 4.
Table 4: Specimen quality
Specimen quality Specimen C Specimen D
Good 5140 (97.35%) 5164 (97.80%)
Leaked 57 (1.08%) 54 (1.02%)
Volume <2 ml 83 (1.57%) 62 (1.12%)
Total 5280 5280
Culture positivity of 93.9% was achieved in the liquid culture system with additional
recovery of 2.2–2.5% from Löwenstein-Jensen (LJ) media backup, which further improved
the culture recovery rates. DST was performed on culture growth from specimens of 3064
(94.57%) patients out of 3240 new TB patients and 1893 (92.79%) out of 2040 previously
treated TB patients as shown in Table 5.
Table 5: Status of DST availability among enrolled patients
New TB patients Previously treated
patients
All patients
Number enrolled 3240 2040 5280
DST Available 3064 (94.57%) 1893 (92.79%) 4957 (93.88%)
3.2 Participant profile
Age and gender distribution is shown in Tables 6 and 7. Seventy-two percent (72.01%) of the
survey participants were males and 27.99% were females. Children in the 0–14 years age
group contributed to 1.7% of the survey population. Though males were predominant in all
age groups in terms of absolute numbers except in the 0–14 years age group, more than
60% of females were aged less than 34 years. The age and gender distribution of survey
participants were similar to the distribution of smear positive TB patients registered in
RNTCP in 2015.
17
Table 6: Gender distribution and type of patients among participants
Gender New TB patients
(%)
Previously
treated patients
(%)
All patients (%)
Female 1,013 (31.37%) 465 (22.79%) 1478 (27.99%)
Male 2227 (68.73%) 1575 (77.97%) 3802 (72.01%)
Total 3240 (100%) 2040 (100%) 5280 (100%)
Table 7: Age distribution and type of patients among participants
3.3 MDR-TB/XDR-TB among new and previously treated TB patients
Among the 4958 TB patients with DST results, 28% had resistance to one or the other anti-
TB drug, while 6.19% had MDR-TB. Among the 307 MDR-TB patients, 11 (3.58%) and 67
(21.82%) patients had additional resistance to any drug from second line injectable class and
any drug from fluoroquinolone class, respectively; i.e. pre-XDR-TB. Thus, among the 78
preXDR-TB patients, most of the patients (67 [86%]) had additional fluoroquinolone
resistance. XDR-TB among MDR-TB patients was 1.3%. (Table 8).
Age group (years) Female (%) Male (%) Total (%)
(0–14) 69 (4.70%) 21 (0.60%) 90 (1.7%)
(15–24) 462 (31.30%) 636 (16.70%) 1098 (20.80%)
(25–34) 377(25.50%) 757 (19.90%) 1134 (21.50%)
(35–44) 211(14.30%) 752(19.80%) 963(18.20%)
(45–54) 155(10.50%) 752 (19.80%) 907(17.20%)
(55–64) 138(9.30%) 541 (14.20%) 679 (12.90%)
65+ 66(4.50%) 343 (9.00%) 409 (7.70%)
18
Table 8: MDR-TB/XDR-TB among new and previously treated TB patients
New TB patients
(95% CI)
Previously treated
patients
(95% CI)
All patients
(95% CI)
DST results 3065 1893 4958
Susceptible
2374 (77.46%)
(75.93–78.92%)
1196 (63.18%)
(60.96–65.36%)
3570 (72.01%)
(70.73–73.25%)
Any DR
691 (22.54%)
(21.10–24.10%)
697 (36.82%)
(34.64–39.04%)
1388 (28.00%)
(26.77–29.29%)
MDR
87 (2.84%)
(2.28–3.49%)
220 (11.62%)
(10.21–13.15%)
307 (6.19%)
(5.54–6.90%)
MDR + any SLI
6 (6.90%)
(2.57–14.41%)
5 (2.27%)
(0.74–5.22%)
11 (3.58%)
(1.80–6.32%)
MDR + any FQ
21 (24.14%)
(15.60–34.50%)
46 (20.91%)
(15.73–26.89%)
67 (21.82%)
(17.33–26.87%)
XDR
2 (2.30%)
(0.28–8.06%)
2 (0.91%)
(0.11–3.25%)
4 (1.30%)
(0.36–3.30%)
Among the 3065 new TB patients subjected to DST for 13 drugs, 2374 (77.46%) were
susceptible to all drugs tested, while 691 (22.54%) showed resistance to any drug. MDR-TB
was detected in 87 (2.84%) of the new TB patients tested as shown in Table 8. Mono
resistance to rifampicin was not observed among new TB patients, thereby indicating that
rifampicin resistance was always accompanied by isoniazid resistance.
3.4 Individual drug resistance pattern among new and previously treated
TB patients
Among the 1893 previously treated TB patients subjected to DST, 1196 (63.18%) were
susceptible to all drugs while 697 (36.82%) showed resistance to any drug. MDR-TB was
detected in 220 (11.62%) patients (Table 9). Mono resistance to rifampicin was observed in
one patient (0.05%) among the previously treated TB patients.
19
Table 9: Individual drug resistance patterns
Drugs New patients Previously treated patients
% any resistance
(95% CI)
% mono
resistance
(95% CI)
% any resistance
(95% CI)
% mono
resistance
(95% CI)
Streptomycin
6.88
(6.01–7.84)
2.22
(1.73–2.81)
13.26
(11.76–14.87)
2.48
(1.83–3.29)
Isoniazid
11.06
(9.97–12.22)
3.85
(3.20–4.60)
25.09
(23.15–27.11)
7.61
(6.45–8.89)
Rifampicin
2.84
(2.28–3.49)
0
(0.0)
11.67
(10.26–13.21)
0.05
(0.001–0.29)
Ethambutol
2.28
(1.78–2.88)
0.23
(0.092–0.47)
7.03
(5.92–8.27)
0.21
(0.06–0.54)
Pyrazinamide
6.95
(6.07–7.91)
4.11
(3.44–4.88)
8.77
(7.53–10.13)
4.07
(3.22–5.06)
Kanamycin
1.01
(0.69–1.43)
0.03
(0.0–0.18)
1.01
(0.61–1.56)
0
(0.0)
Amikacin
0.98
(0.66–1.39)
0.07
(0.01–0.24)
1.01
(0.61–1.56)
0.05
(0.001–0.29)
Capreomycin
1.04
(0.72–1.47)
0.03
(0.02–0.18)
0.85
(0.48–1.37)
0
(0.0)
Ofloxacin
3.72
(3.08–4.45)
0.59
(0.35–0.93)
6.29
(5.23–7.48)
0.95
(0.56–1.50)
Levofloxacin
2.71
(2.16–3.35)
0.1
(0.02–0.29)
3.75
(2.94–4.71)
0
(0.0)
Moxifloxacin
2.58
(2.04–3.20)
0.07
(0.01–0.24)
4.01
(3.18–4.99)
0
(0.0)
Para‐amino
salicylic
sodium
2.32
(1.81–2.91)
0.33
(0.16–0.60)
2.38
(1.74–3.17)
0.42
(0.18–0.83)
Ethionamide
2.54
(2.02–3.17)
0.33
(0.16–0.60)
3.06
(2.33–3.94)
0.26
(0.09–0.62)
20
Drug resistance patterns of M. tuberculosis strains collected from newly diagnosed sputum
smear-positive TB patients
Resistance patterns to individual first-line drugs tested indicated highest resistance to
isoniazid (any 11.06%, mono 3.85%) followed by resistance for pyrazinamide (any 6.95%,
mono 4.11%), streptomycin (any 6.88%, mono 2.22%) and ethambutol (any 2.28%, mono
0.23%) as shown in Table 9.
Resistance patterns to individual second line drugs tested indicated highest resistance to
ofloxacin (any 3.72%, mono 0.59%) followed by resistance for levofloxacin (any 2.71%,
mono 0.1%), moxifloxacin (any 2.58%, mono 0.07%), ethionamide (any 2.54%, mono 0.33%),
para-amino salicylic acid sodium (any 2.32%, mono 0.33%), capreomycin (any 1.04%, mono
0.03%), kanamycin (any 1.01%, mono 0.03%) and amikacin (any 0.98%, mono 0.33%) as
shown in Table 9.
Drug resistance patterns of M. tuberculosis strains collected from previously treated sputum
smear-positive TB patients
Resistance patterns to individual first-line drugs tested indicated highest resistance to
isoniazid (any 25.09%, mono 7.61%) followed by resistance for streptomycin (any 13.26%,
mono 2.48%), pyrazinamide (any 8.77%, mono 4.07%), and ethambutol (any 7.03%, mono
0.21%) as shown in Table 9.
Resistance patterns to individual second line drugs tested indicated highest resistance to
ofloxacin (any 6.29%, mono 0.95%) followed by resistance for moxifloxacin (any 4.01%,
mono 0.0%), levofloxacin (any 3.75%, mono 0.0%), ethionamide (any 3.06%, mono 0.26%),
para-amino salicylic acid sodium (any 2.38%, mono 0.42%), amikacin (any 1.01%, mono
0.05%), kanamycin (any 1.01%, mono 0.0%) and capreomycin (any 0.85%, mono 0.0%) as
shown in Table 9.
3.5 Additional first-line anti-TB drug resistance among confirmed MDR-TB
patients
Among the 87 new TB patients with MDR-TB, any resistance to other first-line drugs was
also observed to be high for streptomycin 70.1% (CI 59.35-79.46%), followed by ethambutol
45.98% (CI 35.23–57.0%), and the least for pyrazinamide 31.03% (21.55–41.86%).
Among the 220 previously treated TB patients with MDR-TB, any resistance to other first-
line drugs was observed to be highest for streptomycin 59.09% (CI 52.28–65.65%), followed
by ethambutol 46.36% (CI 39.64–53.19%) and the least for pyrazinamide 20.45% (CI 15.33–
26.40%).
21
3.6 Additional second line anti-TB drug resistance among confirmed MDR-
TB patients
Amongst the 87 new TB patients with MDR-TB, 21 (24.14%) had additional resistance to any
fluoroquinolone and 6 (6.90%) to any second line injectable drugs. XDR-TB was observed in
2 (2.30%) patients among MDR-TB patients (Table 8). Further, any resistance to other
second line drugs was observed to be highest for ofloxacin 24.14% (CI 15.6–34.5%), followed
by moxifloxacin 18.39% (CI 10.89–28.14%), levofloxacin 17.24% (CI 9.98–26.84%),
ethionamide and PAS 11.49% (CI 5.65–20.12%) each, amikacin and capreomycin 8.05% (CI
3.3–15.88%) each and the least for kanamycin 4.6% (CI 1.27–11.36%).
Among the previously treated TB patients with MDR-TB, 46 (20.91%) had additional
resistance to any fluoroquinolone and 5 (2.27%) to any second line injectable drugs. XDR-TB
was observed in 2 (0.91%) patients (Table 8). Further, any resistance to other second line
drugs was observed to be highest for ofloxacin 21.36% (CI 16.14–27.38%), followed by
moxifloxacin 15.45% (CI 10.95–20.92%), levofloxacin 14.09% (CI 9.78–19.40%), ethionamide
7.27% (CI 4.21–11.55%), PAS 4.09% (CI 1.89–7.62%), kanamycin and amikacin 2.27% (CI
0.74–5.22%) each and the least for capreomycin 1.81% (CI 0.49–4.59%).
3.7 DR-TB rates among states
Sample size for the survey was calculated for obtaining national level estimates only and
State level inferences cannot be drawn directly from the survey. However, resistance to any
drug as well as distribution of MDR among the States that participated suggests areas for
focus action. State-wise drug resistance rates are given in Table 10 using the numbers
collected from each state that provided specimens for the survey.
A state level analysis of drug resistance indicates that DR-TB is prevalent in all states, albeit
with wide variations ranging from 18.42% in Himachal Pradesh to 36.84% in Jammu &
Kashmir. In addition, this is an indication that screening of drug resistance has to be
expanded to offer universal DST including expanded DST as envisaged in the updated PMDT
guidelines. The second and most important activity is to strengthen drug resistance
surveillance under the programme with inclusion of laboratories in the private sector as
well. The state levels rates also give us the opportunity to plan and execute intervention
prioritizing, based on the drug resistance trends observed.
22
Table 10: DR-TB rates among different states in India
State
New TB patients Previously treated TB patients
TotalDST
result
MDR
%MDR
DR(other
thanMDR)
%DR(other
thanMDR)
TotalDST
result
MDR
%MDR
DR(other
thanMDR)
%DR(other
thanMDR)
Andhra Pradesh
183 1 0.55 40 21.86 114 9 7.89 25 21.93
Assam
79 2 2.53 20 25.32 48 2 4.17 16 33.33
Bihar
177 8 4.52 32 18.08 109 16 14.68 22 20.18
Chhattisgarh
47 2 4.26 9 19.15 33 2 6.06 11 33.33
Delhi
80 1 1.25 17 21.25 46 4 8.70 13 28.26
Gujarat
183 3 1.64 26 14.21 113 6 5.31 17 15.04
Haryana
53 0 0.00 6 11.32 31 4 12.90 11 35.48
Himachal Pradesh
23 1 4.35 2 8.70 15 0 0.00 4 26.67
Jammu & Kashmir
26 0 0.00 7 26.92 12 0 0.00 7 58.33
Jharkhand
103 2 1.94 13 12.62 62 7 11.29 13 20.97
Karnataka
128 0 0.00 37 28.91 81 1 1.23 24 29.63
Kerala
53 1 1.89 9 16.98 27 3 11.11 5 18.52
Madhya Pradesh
142 3 2.11 25 17.61 88 9 10.23 28 31.82
Maharashtra
259 20 7.72 50 19.31 161 19 11.80 41 25.47
Meghalaya
24 0 0.00 6 25.00 15 2 13.33 1 6.67
Nagaland
26 1 3.85 4 15.38 16 2 12.50 6 37.50
Orissa
106 0 0.00 27 25.47 66 7 10.61 17 25.76
Punjab
78 1 1.28 10 12.82 46 2 4.35 15 32.61
Rajasthan
179 5 2.79 34 18.99 116 15 12.93 33 28.45
Sikkim
25 1 4.00 6 24.00 17 3 17.65 2 11.76
Tamil Nadu
138 4 2.90 21 15.22 90 7 7.78 24 26.67
Telangana
53 0 0.00 16 30.19 33 5 15.15 7 21.21
Uttar Pradesh
640 29 4.53 133 20.78 399 79 19.80 96 24.06
Uttarakhand
54 1 1.85 12 22.22 30 6 20.00 7 23.33
West Bengal
205 1 0.49 42 20.49 125 10 8.00 32 25.60
Total
3064 87 2.84 604 19.71 1893 220 11.62 477 25.20
23
3.8 Conclusions
Key findings
 Among all TB patients tested, MDR-TB rate was 6.19% with 2.84% among new and
11.60% among previously treated TB patients.
 Any isoniazid resistance among new and previously treated TB patients was 11.06%
and 25.09%, respectively.
 Any drug resistance among new TB patients was 22.54%, with 36.82% among
previously treated TB patients and 28.02% among all patients.
 There was negligible rifampicin mono-resistance in the survey and isoniazid
resistance was invariably associated with rifampicin resistance. Any pyrazinamide
resistance was 6.95% and 8.77% among new and previously treated TB patients,
respectively.
 Among MDR-TB patients, additional resistance to any fluoroquinolone was 21% and
any second line drug resistance was 3.84%.
 Among MDR-TB patients, XDR-TB rate was 1.3%.
 There were wide variations in the state-wise levels of drug resistance (Table 10),
highlighting that national level estimates tends to mask the local and focal epidemics
that need to be addressed with specific interventions.
Key steps going forward
The key next steps are:
 Setting up and strengthening drug resistance surveillance including using state of art
next generation sequencing. This will provide the programme with the trends of drug
resistance, transmission patterns and mapping of hot spots in different states for
better understanding of molecular epidemiology for TB surveillance.
 Rapidly scaling up universal DST and appropriate DST guided treatment.
 Strengthening epidemiologic intelligence for specific interventions based on local
epidemiological profile.
24
References
1. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016
(www.who.int/tb/publications/global_report, accessed 19 December 2017).
2. World Lung Conference 2010 – Association of poor culture conversion with fluoroquinolone
resistance in Gujarat, Western India..R.N. Solanki, P V Dave, T V Bhalodia, S Chadha, F Wares,
N Selvakumar, L S Chauhan, P Dewan
3. Surveillance of drug-resistant tuberculosis in the state of Gujarat, India. Ramachandran R,
Nalini S, Chandrasekar V, Dave PV, Sanghvi AS, Wares F, et al. Int J Tuberc Lung Dis.
2009;13(9):1154–60.
4. Siddiqui SH, Rüsch-Gerdes S. MGITTM
Procedure Manual. Geneva: Foundation for Innovative
New Diagnostics; 2006.
5. Revised National TB Control Programme Training Manual for Mycobacterium tuberculosis
Culture & Drug susceptibility testing. https://tbcindia.gov.in/showfile.php?lid=2991
6. Policy guidance on drug-susceptibility testing (DST) of second-line anti-tuberculosis drugs.
Geneva: World Health Organization; 2008 (WHO/HTM/TB/2008.392, accessed 19 December
2017).
7. Guidelines for surveillance of drug resistance in tuberculosis - 5th edition. Geneva: World
Health Organization; 2015 (WHO/HTM/TB/2015.13, accessed 19 December 2017).
Report of the First National Anti TB Drug Resistance Survey India
Report of the First National Anti TB Drug Resistance Survey India

Weitere ähnliche Inhalte

Was ist angesagt?

To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
 
JTR_2016081815424293 (1)
JTR_2016081815424293 (1)JTR_2016081815424293 (1)
JTR_2016081815424293 (1)Hamdan Hamdan
 
Reasons for innovations and changing strategies in RNTCP 2019
Reasons for innovations and changing strategies in RNTCP 2019Reasons for innovations and changing strategies in RNTCP 2019
Reasons for innovations and changing strategies in RNTCP 2019Drsadhana Meena
 
Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...
Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...
Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...DrHeena tiwari
 
IOSR Journal of Pharmacy (IOSRPHR)
IOSR Journal of Pharmacy (IOSRPHR)IOSR Journal of Pharmacy (IOSRPHR)
IOSR Journal of Pharmacy (IOSRPHR)iosrphr_editor
 
Diagnosis and management of tuberculosis with revised rntcp
Diagnosis and management of tuberculosis with revised rntcpDiagnosis and management of tuberculosis with revised rntcp
Diagnosis and management of tuberculosis with revised rntcpDrPrincePrakash
 
SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...
SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...
SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...Earthjournal Publisher
 
Necessity of COVID-19 vaccination in previously infected individuals
Necessity of COVID-19 vaccination in previously infected individualsNecessity of COVID-19 vaccination in previously infected individuals
Necessity of COVID-19 vaccination in previously infected individualsMattisHallsteinVolla
 
Взаимовыгодная реклама - Осенние скидки
Взаимовыгодная реклама - Осенние скидкиВзаимовыгодная реклама - Осенние скидки
Взаимовыгодная реклама - Осенние скидкиmycasio
 
A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19
A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19
A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19Valentina Corona
 

Was ist angesagt? (19)

DU in Burn Population (1)
DU in Burn Population (1)DU in Burn Population (1)
DU in Burn Population (1)
 
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
 
Priyakant_Author_PLOS
Priyakant_Author_PLOSPriyakant_Author_PLOS
Priyakant_Author_PLOS
 
JTR_2016081815424293 (1)
JTR_2016081815424293 (1)JTR_2016081815424293 (1)
JTR_2016081815424293 (1)
 
Reasons for innovations and changing strategies in RNTCP 2019
Reasons for innovations and changing strategies in RNTCP 2019Reasons for innovations and changing strategies in RNTCP 2019
Reasons for innovations and changing strategies in RNTCP 2019
 
Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...
Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...
Knowledge and Attitude of Prosthodontic Post Graduates on COVID 19: A Qualita...
 
IOSR Journal of Pharmacy (IOSRPHR)
IOSR Journal of Pharmacy (IOSRPHR)IOSR Journal of Pharmacy (IOSRPHR)
IOSR Journal of Pharmacy (IOSRPHR)
 
Diagnosis and management of tuberculosis with revised rntcp
Diagnosis and management of tuberculosis with revised rntcpDiagnosis and management of tuberculosis with revised rntcp
Diagnosis and management of tuberculosis with revised rntcp
 
Deepak rntcp
Deepak rntcpDeepak rntcp
Deepak rntcp
 
SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...
SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...
SPORADIC OUTBREAK CASES OF DIPHTHERIA: A THREE YEARS’ STUDY IN A TERTIARY CAR...
 
256th publication jpbs- 7th name
256th publication  jpbs- 7th name256th publication  jpbs- 7th name
256th publication jpbs- 7th name
 
Imjh mar-2015-6
Imjh mar-2015-6Imjh mar-2015-6
Imjh mar-2015-6
 
Necessity of COVID-19 vaccination in previously infected individuals
Necessity of COVID-19 vaccination in previously infected individualsNecessity of COVID-19 vaccination in previously infected individuals
Necessity of COVID-19 vaccination in previously infected individuals
 
178th publication jfmpc- 7th name
178th publication  jfmpc- 7th name178th publication  jfmpc- 7th name
178th publication jfmpc- 7th name
 
Взаимовыгодная реклама - Осенние скидки
Взаимовыгодная реклама - Осенние скидкиВзаимовыгодная реклама - Осенние скидки
Взаимовыгодная реклама - Осенние скидки
 
10.1093@cid@cix505
10.1093@cid@cix50510.1093@cid@cix505
10.1093@cid@cix505
 
A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19
A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19
A trial of Lopinavir-Ritonavir in Adults Hospitalized with Sever COVID-19
 
RNTCP 2019
RNTCP 2019RNTCP 2019
RNTCP 2019
 
182nd publication jamdsr- 6th name
182nd publication  jamdsr- 6th name182nd publication  jamdsr- 6th name
182nd publication jamdsr- 6th name
 

Ähnlich wie Report of the First National Anti TB Drug Resistance Survey India

RNTCP.pptx revised national tuberculosis program
RNTCP.pptx revised national tuberculosis programRNTCP.pptx revised national tuberculosis program
RNTCP.pptx revised national tuberculosis programSupriyaBatwalkar
 
TB Preventive Therapy
TB Preventive TherapyTB Preventive Therapy
TB Preventive TherapyRivu Basu
 
An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...
An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...
An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...Allison Thompson
 
07-Presentation1
07-Presentation107-Presentation1
07-Presentation1manish joya
 
Drug resistant tuberculosis: A diagnostic challenge
Drug resistant tuberculosis: A diagnostic challengeDrug resistant tuberculosis: A diagnostic challenge
Drug resistant tuberculosis: A diagnostic challengeDr Muktikesh Dash, MD, PGDFM
 
High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...
High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...
High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...Madiha Mushtaque
 
critical review RNTCP
critical review RNTCPcritical review RNTCP
critical review RNTCPHar Jindal
 
IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...
IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...
IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...Dr Dhanji Rajani
 
Multi drug resistant tuberculosis
Multi drug resistant tuberculosisMulti drug resistant tuberculosis
Multi drug resistant tuberculosisMelaku Yetbarek,MD
 
The prevalence and treatment of tuberculosis (TB) in primary health care sett...
The prevalence and treatment of tuberculosis (TB) in primary health care sett...The prevalence and treatment of tuberculosis (TB) in primary health care sett...
The prevalence and treatment of tuberculosis (TB) in primary health care sett...SriramNagarajan17
 
Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...
Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...
Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...Dr.Samsuddin Khan
 
Facilitor's guide for cv training draft1
Facilitor's guide for cv training  draft1Facilitor's guide for cv training  draft1
Facilitor's guide for cv training draft1Abhijit Dey
 
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013hivlifeinfo
 
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013Hivlife Info
 
PlosOne_EarlyOutcomes_RRTBTx.PDF
PlosOne_EarlyOutcomes_RRTBTx.PDFPlosOne_EarlyOutcomes_RRTBTx.PDF
PlosOne_EarlyOutcomes_RRTBTx.PDFErika Mohr
 

Ähnlich wie Report of the First National Anti TB Drug Resistance Survey India (20)

RNTCP.pptx revised national tuberculosis program
RNTCP.pptx revised national tuberculosis programRNTCP.pptx revised national tuberculosis program
RNTCP.pptx revised national tuberculosis program
 
TB Preventive Therapy
TB Preventive TherapyTB Preventive Therapy
TB Preventive Therapy
 
An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...
An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...
An Overview Of Programmatic Management Of Drug Resistance Tuberculosis (PMDT)...
 
07-Presentation1
07-Presentation107-Presentation1
07-Presentation1
 
Drug resistant tuberculosis: A diagnostic challenge
Drug resistant tuberculosis: A diagnostic challengeDrug resistant tuberculosis: A diagnostic challenge
Drug resistant tuberculosis: A diagnostic challenge
 
High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...
High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...
High prevalence of DR-TB (drug-resistant tuberculosis): An Indicator of publi...
 
Journal mdr tb outcome
Journal mdr tb outcomeJournal mdr tb outcome
Journal mdr tb outcome
 
Tuberculosis among household contacts of multidrug resistant tuberculosis cas...
Tuberculosis among household contacts of multidrug resistant tuberculosis cas...Tuberculosis among household contacts of multidrug resistant tuberculosis cas...
Tuberculosis among household contacts of multidrug resistant tuberculosis cas...
 
critical review RNTCP
critical review RNTCPcritical review RNTCP
critical review RNTCP
 
IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...
IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...
IN VITRO STUDY OF A MULTI DRUG RESISTANT MYCOBACTERIA AND EFFECT OF HERBAL DR...
 
Multi drug resistant tuberculosis
Multi drug resistant tuberculosisMulti drug resistant tuberculosis
Multi drug resistant tuberculosis
 
The prevalence and treatment of tuberculosis (TB) in primary health care sett...
The prevalence and treatment of tuberculosis (TB) in primary health care sett...The prevalence and treatment of tuberculosis (TB) in primary health care sett...
The prevalence and treatment of tuberculosis (TB) in primary health care sett...
 
Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...
Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...
Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral...
 
Facilitor's guide for cv training draft1
Facilitor's guide for cv training  draft1Facilitor's guide for cv training  draft1
Facilitor's guide for cv training draft1
 
02. hiv dr di indonesia
02. hiv dr di indonesia02. hiv dr di indonesia
02. hiv dr di indonesia
 
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
 
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
Recent Advances in Multidrug-Resistant TB of HIV/TB coinfection.2013
 
PlosOne_EarlyOutcomes_RRTBTx.PDF
PlosOne_EarlyOutcomes_RRTBTx.PDFPlosOne_EarlyOutcomes_RRTBTx.PDF
PlosOne_EarlyOutcomes_RRTBTx.PDF
 
Piis1473 3099(16)30190-6
Piis1473 3099(16)30190-6Piis1473 3099(16)30190-6
Piis1473 3099(16)30190-6
 
MDR - XDR
MDR - XDRMDR - XDR
MDR - XDR
 

Mehr von Anup Soans

An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...
An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...
An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...Anup Soans
 
Key Challenges Facing Pharma Industry and the Way Forward
Key Challenges Facing Pharma Industry and the Way ForwardKey Challenges Facing Pharma Industry and the Way Forward
Key Challenges Facing Pharma Industry and the Way ForwardAnup Soans
 
Trends in Pharma Marketing - Focus and Spending
Trends in Pharma Marketing - Focus and SpendingTrends in Pharma Marketing - Focus and Spending
Trends in Pharma Marketing - Focus and SpendingAnup Soans
 
MedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27th
MedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27thMedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27th
MedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27thAnup Soans
 
Key Account Management - Time for India Pharma to Adopt KAM
Key Account Management - Time for India Pharma to Adopt KAMKey Account Management - Time for India Pharma to Adopt KAM
Key Account Management - Time for India Pharma to Adopt KAMAnup Soans
 
MedicinMan Report on Digital Readiness of Indian Pharma 2021
MedicinMan Report on Digital Readiness of Indian Pharma 2021MedicinMan Report on Digital Readiness of Indian Pharma 2021
MedicinMan Report on Digital Readiness of Indian Pharma 2021Anup Soans
 
How can Pharma Use Digital to Engage Doctors and Understand Patients
How can Pharma Use Digital to Engage Doctors and Understand PatientsHow can Pharma Use Digital to Engage Doctors and Understand Patients
How can Pharma Use Digital to Engage Doctors and Understand PatientsAnup Soans
 
Why Indian Pharma Needs to Enable Managers to Develop Talent
Why Indian Pharma Needs to Enable Managers to Develop TalentWhy Indian Pharma Needs to Enable Managers to Develop Talent
Why Indian Pharma Needs to Enable Managers to Develop TalentAnup Soans
 
Digital Excellence Pharma Academy Certification Program
Digital Excellence Pharma Academy Certification ProgramDigital Excellence Pharma Academy Certification Program
Digital Excellence Pharma Academy Certification ProgramAnup Soans
 
Digital Excellent Pharma Academy Certification Program
Digital Excellent Pharma Academy Certification ProgramDigital Excellent Pharma Academy Certification Program
Digital Excellent Pharma Academy Certification ProgramAnup Soans
 
COVID-19 Vaccine Roll Out Plan by Ministry of Health and Family Affairs
COVID-19 Vaccine Roll Out Plan by Ministry of Health and Family AffairsCOVID-19 Vaccine Roll Out Plan by Ministry of Health and Family Affairs
COVID-19 Vaccine Roll Out Plan by Ministry of Health and Family AffairsAnup Soans
 
Architecture To Develop Pharma Business Leaders For Today and Tomorrow
Architecture To Develop Pharma Business Leaders  For Today and Tomorrow  Architecture To Develop Pharma Business Leaders  For Today and Tomorrow
Architecture To Develop Pharma Business Leaders For Today and Tomorrow Anup Soans
 
What is Indian Pharma Thinking about Digital? A Research Project
What is Indian Pharma Thinking about Digital? A Research ProjectWhat is Indian Pharma Thinking about Digital? A Research Project
What is Indian Pharma Thinking about Digital? A Research ProjectAnup Soans
 
Digital Excellence Pharma Academy - Webinar & Online Certification Program
Digital Excellence Pharma Academy - Webinar & Online Certification ProgramDigital Excellence Pharma Academy - Webinar & Online Certification Program
Digital Excellence Pharma Academy - Webinar & Online Certification ProgramAnup Soans
 
Telemedicine Guidelines for Indian Doctors
Telemedicine Guidelines for Indian DoctorsTelemedicine Guidelines for Indian Doctors
Telemedicine Guidelines for Indian DoctorsAnup Soans
 
The Mankind Pharma Story by Dr. Sumit Ghoshal
The Mankind Pharma Story by Dr. Sumit GhoshalThe Mankind Pharma Story by Dr. Sumit Ghoshal
The Mankind Pharma Story by Dr. Sumit GhoshalAnup Soans
 
Indian Pharma and Retail Pharmacies - Sales View Poll
Indian Pharma and Retail Pharmacies - Sales View PollIndian Pharma and Retail Pharmacies - Sales View Poll
Indian Pharma and Retail Pharmacies - Sales View PollAnup Soans
 
Healthcare's Future will be Patient Experience
Healthcare's Future will be Patient ExperienceHealthcare's Future will be Patient Experience
Healthcare's Future will be Patient ExperienceAnup Soans
 
Unethical Practices in Pharma - Interesting Study from Pakistan
Unethical Practices in Pharma - Interesting Study from Pakistan Unethical Practices in Pharma - Interesting Study from Pakistan
Unethical Practices in Pharma - Interesting Study from Pakistan Anup Soans
 
MedicinMan December 2018 Issue
MedicinMan December 2018 IssueMedicinMan December 2018 Issue
MedicinMan December 2018 IssueAnup Soans
 

Mehr von Anup Soans (20)

An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...
An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...
An Infectious Disease Specialist, Dr Mandar Kubal Speaks to Pharma on How it ...
 
Key Challenges Facing Pharma Industry and the Way Forward
Key Challenges Facing Pharma Industry and the Way ForwardKey Challenges Facing Pharma Industry and the Way Forward
Key Challenges Facing Pharma Industry and the Way Forward
 
Trends in Pharma Marketing - Focus and Spending
Trends in Pharma Marketing - Focus and SpendingTrends in Pharma Marketing - Focus and Spending
Trends in Pharma Marketing - Focus and Spending
 
MedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27th
MedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27thMedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27th
MedicinMan CEO Roundtable 2021 is here... Saturday, Feb 27th
 
Key Account Management - Time for India Pharma to Adopt KAM
Key Account Management - Time for India Pharma to Adopt KAMKey Account Management - Time for India Pharma to Adopt KAM
Key Account Management - Time for India Pharma to Adopt KAM
 
MedicinMan Report on Digital Readiness of Indian Pharma 2021
MedicinMan Report on Digital Readiness of Indian Pharma 2021MedicinMan Report on Digital Readiness of Indian Pharma 2021
MedicinMan Report on Digital Readiness of Indian Pharma 2021
 
How can Pharma Use Digital to Engage Doctors and Understand Patients
How can Pharma Use Digital to Engage Doctors and Understand PatientsHow can Pharma Use Digital to Engage Doctors and Understand Patients
How can Pharma Use Digital to Engage Doctors and Understand Patients
 
Why Indian Pharma Needs to Enable Managers to Develop Talent
Why Indian Pharma Needs to Enable Managers to Develop TalentWhy Indian Pharma Needs to Enable Managers to Develop Talent
Why Indian Pharma Needs to Enable Managers to Develop Talent
 
Digital Excellence Pharma Academy Certification Program
Digital Excellence Pharma Academy Certification ProgramDigital Excellence Pharma Academy Certification Program
Digital Excellence Pharma Academy Certification Program
 
Digital Excellent Pharma Academy Certification Program
Digital Excellent Pharma Academy Certification ProgramDigital Excellent Pharma Academy Certification Program
Digital Excellent Pharma Academy Certification Program
 
COVID-19 Vaccine Roll Out Plan by Ministry of Health and Family Affairs
COVID-19 Vaccine Roll Out Plan by Ministry of Health and Family AffairsCOVID-19 Vaccine Roll Out Plan by Ministry of Health and Family Affairs
COVID-19 Vaccine Roll Out Plan by Ministry of Health and Family Affairs
 
Architecture To Develop Pharma Business Leaders For Today and Tomorrow
Architecture To Develop Pharma Business Leaders  For Today and Tomorrow  Architecture To Develop Pharma Business Leaders  For Today and Tomorrow
Architecture To Develop Pharma Business Leaders For Today and Tomorrow
 
What is Indian Pharma Thinking about Digital? A Research Project
What is Indian Pharma Thinking about Digital? A Research ProjectWhat is Indian Pharma Thinking about Digital? A Research Project
What is Indian Pharma Thinking about Digital? A Research Project
 
Digital Excellence Pharma Academy - Webinar & Online Certification Program
Digital Excellence Pharma Academy - Webinar & Online Certification ProgramDigital Excellence Pharma Academy - Webinar & Online Certification Program
Digital Excellence Pharma Academy - Webinar & Online Certification Program
 
Telemedicine Guidelines for Indian Doctors
Telemedicine Guidelines for Indian DoctorsTelemedicine Guidelines for Indian Doctors
Telemedicine Guidelines for Indian Doctors
 
The Mankind Pharma Story by Dr. Sumit Ghoshal
The Mankind Pharma Story by Dr. Sumit GhoshalThe Mankind Pharma Story by Dr. Sumit Ghoshal
The Mankind Pharma Story by Dr. Sumit Ghoshal
 
Indian Pharma and Retail Pharmacies - Sales View Poll
Indian Pharma and Retail Pharmacies - Sales View PollIndian Pharma and Retail Pharmacies - Sales View Poll
Indian Pharma and Retail Pharmacies - Sales View Poll
 
Healthcare's Future will be Patient Experience
Healthcare's Future will be Patient ExperienceHealthcare's Future will be Patient Experience
Healthcare's Future will be Patient Experience
 
Unethical Practices in Pharma - Interesting Study from Pakistan
Unethical Practices in Pharma - Interesting Study from Pakistan Unethical Practices in Pharma - Interesting Study from Pakistan
Unethical Practices in Pharma - Interesting Study from Pakistan
 
MedicinMan December 2018 Issue
MedicinMan December 2018 IssueMedicinMan December 2018 Issue
MedicinMan December 2018 Issue
 

Kürzlich hochgeladen

FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...Shubhanshu Gaurav
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyZurück zum Ursprung
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communicationskatiequigley33
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.whalesdesign
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfHongBiThi1
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismusChandrasekar Reddy
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdfHongBiThi1
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptPradnya Wadekar
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisSujoy Dasgupta
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfHongBiThi1
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 

Kürzlich hochgeladen (20)

FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturally
 
Using Data Visualization in Public Health Communications
Using Data Visualization in Public Health CommunicationsUsing Data Visualization in Public Health Communications
Using Data Visualization in Public Health Communications
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismus
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologyppt
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosis
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 

Report of the First National Anti TB Drug Resistance Survey India

  • 7. i List of contributors Survey team Principal investigators: Dr Jagdish Prasad, Director General Health Services, Dte GHS, MoHFW; Dr Prahlad Kumar, National Tuberculosis Institute, Bangalore, Dte GHS, MoHFW Co-principal investigator: Dr Ranjani Ramachandran, WHO Country Office for India Team members who contributed to the survey Protocol development: Dr S. Anand, Dr Malik Parmar, Dr Kiran Rade, Dr Puneet Dewan, Dr Patrick Moonan Laboratory services: Dr R. Lakshmi, Dr S. Lakshmi and the team of technologists at NTI Data collection and software: Mr Jitendra Suryavamshi Quality assurance for laboratory: National Institute for Research in Tuberculosis, Chennai and SRL Antwerp, Belgium Data analysis and data quality management: Dr A.N. Sreenivas, Dr Malik Parmar, Dr Kiran Rade, Dr Puneet Dewan, Mr Matteo Zignol, Mr C. Sismanidis Programme support: DDG TB, ADDG TB, State TB Officers, District TB Officers and WHO- RNTCP Technical Support Network
  • 9. ii Abbreviations CBNAAT cartridge-based nucleic acid amplification test CIF clinical information form DEFF design effect DMC designated microscopy centre DRS drug resistance survey DR-TB drug-resistant TB IQC internal quality control M. tuberculosis Mycobacterium tuberculosis MDR-TB multidrug-resistant TB MGIT mycobacteria growth indicator tube NDRS National Anti-tuberculosis Drug Resistance Survey NIRT National Institute for Research in Tuberculosis NTI National Tuberculosis Institute PLHIV people living with human immunodeficiency virus PMDT programmatic management of drug-resistant TB QA quality assurance RNTCP Revised National Tuberculosis Control Programme RR-TB rifampicin-resistant TB SRL Supranational Reference Laboratory STLS senior TB laboratory supervisor STS senior treatment supervisor TB tuberculosis TU TB unit WHO World Health Organization XDR-TB extensively drug-resistant TB
  • 11. 1 Executive summary India has more new tuberculosis (TB) patients annually than any other country globally, contributing to 27% of the world’s TB burden. About 2.79 million TB patients are estimated to be added annually. The Revised National Tuberculosis Control Programme (RNTCP) notified around 1.94 million TB patients in 2016 (1). As per the Global TB Report 2017 (1), worldwide approximately 4.1% of new TB patients and 19% of previously treated TB patients have multidrug resistant-TB (MDR-TB), i.e. TB resistant to at least two of the first-line drugs – isoniazid and rifampicin. Extensively drug- resistant TB (XDR-TB), defined as MDR-TB with additional resistance to at least one fluoroquinolone and one second line injectable drug, has been reported by 123 countries. The proportion of XDR-TB among MDR-TB patients is 6.2% worldwide. The estimated number of MDR/rifampicin resistant (RR)-TB in India is 147 000, accounting for one fourth of the global burden of MDR/RR-TB (1). India initiated the programmatic management of drug resistant TB (PMDT) in 2007 to address the emerging problem of drug resistant-TB (DR-TB), and the national PMDT scale-up was achieved by March 2013. The treatment success rate among MDR-TB patients in India is consistently about 46% and the death rate is around 20%, as against the global level of treatment success rate of 52% and death rate of 17%. High rates of treatment failure and deaths are associated with fluoroquinolone resistance in the Indian cohort of MDR-TB patients (2). India has sub-national data from state level anti-TB drug resistant surveys conducted in the past (3); However the epidemiology of DR-TB in India has never been studied nationally. Knowing the epidemiology of DR-TB is essential to guide development of evidence-based strategies to combat DR-TB in India. In view of the above, the Government of India decided to conduct a National Anti-TB Drug Resistance Survey (NDRS) to know the prevalence of drug resistance among TB patients with particular focus on MDR-TB among both new and previously treated TB patients. This is the largest ever NDRS conducted by any country in the world and the first ever survey having drug susceptibility testing (DST) for 13 anti-TB drugs using the automated liquid culture system, mycobacteria growth indicator tube (MGIT) 960®. A total of 5280 sputum smear-positive pulmonary TB patients (3240 new and 2040 previously treated) diagnosed at the designated microscopy centres (DMCs) of RNTCP were enrolled in the survey.
  • 12. 2 The results of the survey showed that:  MDR-TB is 6.19% (CI 5.54–6.90%) among all TB patients with 2.84% (CI 2.27–3.50%) among new and 11.60% (CI 10.21–13.15%) among previously treated TB patients.  Among MDR-TB patients, additional resistance to any fluoroquinolones was 21.82% (17.33–26.87%), and 3.58% (1.8–6.32%) to any second-line injectable drugs.  Among MDR-TB patients, additional resistance to at least one drug from each of the two classes, i.e. fluoroquinolone and second-line injectable drugs (XDR-TB) was 1.3% (0.36–3.30%).  Any first- or second line drug resistance among all TB patients is 28.0% (CI 26.77– 29.29%) with 22.54% (CI 21.10–24.10%) among new and 36.82% (CI 34.64–39.04%) among previously treated TB patients.  Any isoniazid resistance is 11.06% (CI 9.97–12.22%) and 25.09% (CI 23.1–-27.11%) among new and previously treated TB patients, respectively.  Any pyrazinamide resistance is 6.95% (CI 6.07–7.91%) and 8.77% (7.53–10.13%) among new and previously treated TB patients, respectively. MDR-TB rates at the national level are still within the range of previous state-level surveys conducted in India. However, more than a quarter of TB patients in India have drug resistance to one or the other anti-TB drug. Fluoroquinolone resistance among MDR-TB patients is high and is similar to resistance rates reported by the RNTCP. The survey results clearly indicate that drug resistance is present in all settings, and the wide range of resistance patterns from any isoniazid resistance to XDR-TB needs to be addressed with strengthening of drug resistance surveillance, universal DST and appropriate DST guided treatment strategies.
  • 13. 3 1. Introduction 1.1 Country profile With a population of 1.32 billion, India has the highest burden of tuberculosis (TB) and drug- resistant TB (DR-TB) in the world. The Global TB Report 2017 published by World Health Organization (WHO) estimates that India contributes 27% (2.79 million) and 25% (147 000) of the global burden of TB and multi-drug resistant TB (MDR-TB), respectively (1). The Revised National Tuberculosis Control Programme (RNTCP) has notified 1.94 million patients in 2016 (1). India has been locating and treating MDR-TB patients since 2007 and achieved complete geographical coverage of programmatic management of drug-resistant TB (PMDT) services in 2013. Up till 2016, 1 413 331 TB patients have been tested for drug resistance and 139 369 MDR/rifampicin-resistant (RR)-TB cases had been detected in India. Among them, 126 136 MDR/RR-TB and 6377 extensively drug-resistant (XDR)-TB patients have been put on treatment. In 2016 alone, 580 438 TB patients have been tested, 37 358 MDR/RR-TB have been diagnosed and 32 914 MDR/RR-TB and 2475 XDR-TB patients have been put on treatment in India (1). These numbers would increase in years to come as India has initiated implementation of the policy of universal drug-susceptibility testing (DST) in phases since mid-2017. 1.2 Statement of the problem There have been a number of reports in the past on drug resistance in India A majority of them used non-standardized methodologies, biased samples, and were usually conducted at tertiary-level care facilities. However, there is data generated through clinical trials conducted in Tuberculosis Research Centre (now National Institute for Research in Tuberculosis [NIRT]), Chennai where rates of RR-TB and MDR-TB are available from the early 1980s from continuous surveillance of rifampicin resistance. This has been slowly increasing from 0% to 2% among new TB patients till date (Fig. 1). This graph shows the rates of drug resistance including MDR-TB. MDR-TB has been increasing from less than 1% in the early nineties to 2.0% in 2006. Since then, the rates of MDR-TB have been almost static. (Data from 2007 onwards is not shown in Fig. 1).
  • 14. 4 Fig. 1: Trend of first-line anti-TB drug resistance from historical surveys H – Isoniazid; S- Streptomycin; SH – Streptomycin + Isoniazid; HR – Isoniazid + Rifampicin In addition, valid state-level information about the extent of drug resistance is also available (Table 1). These drug resistance surveys (DRSs) were conducted in accordance with standard international protocol. Specimens were collected from a population-based sample of sputum smear-positive patients diagnosed at RNTCP designated microscopy centres (DMCs). Most of the state level surveys conducted in India have also reported patients of XDR-TB. State representative DRSs in Andhra Pradesh and Gujarat (3) showed 4–6% XDR-TB cases among MDR-TB isolates, with a high prevalence of fluoroquinolone resistance ranging from 21% to 25%. Table 1: Rates of MDR-TB – state level surveys Surveys, year and population New patients Previously treated patients Tamil Nadu State, 1997–1998 (60 million) 3.4% 25.0% Gujarat State, 2007–2008 (56 million) (3) 2.4% 17.4% Maharashtra State, 2008 (108 million) 2.7% 14.0% Undivided Andhra Pradesh State, 2009 (86 million) 1.8% 11.8% Tamil Nadu State, 2011 (77 million) (unpublished) 1.8% 13.2% Current knowledge on MDR-TB in India During the initial phase of PMDT implementation, RNTCP offered DST to TB patients who were at the highest risk for MDR-TB, such as treatment failures and contacts of MDR-TB. As the diagnostic capacity increased, the offer of DST was expanded to cover TB patients with moderate/lower risk of MDR-TB. RNTCP continued to expand its DST coverage over the years to test most TB patients with upfront cartridge-based nucleic acid amplification test (CBNAAT) (Xpert MTB/RIF) followed by baseline second line DST, and has embarked upon phased implementation of universal DST since mid-2017. 0 2 4 6 8 10 12 14 16 18 56-57 57-58 61- 61-62 62-63 63-66 67-68 68-69 70-72 72-74 74-77 77-80 80-85 85-86 86-90 90-95 95-9898-20012001-032004-06 H S SH HR
  • 15. 5 Apart from DST, CBNAAT is also offered for diagnosis of TB in key populations like people living with human immunodeficiency virus (PLHIV), children, those with extra-pulmonary signs/symptoms and smear negative patients with chest X-ray suggestive of TB, for microbiological confirmation of TB. The rates of MDR/RR-TB observed over the past decade in the programme as the DST offer expanded from highest risk cases to those at least risk of MDR-TB are shown in Table 2. Table 2: MDR/RR-TB reported by RNTCP (PMDT services) Rationale India is one of the highest burden countries for TB and MDR-TB. However, the epidemiology of DR-TB in India has never been studied nationally. This is essential to measure the DR-TB burden and to guide development of evidence-based strategies to combat DR-TB in India. In view of the above, the Government of India decided to conduct a National Anti-Tuberculosis Drug Resistance Survey (NDRS) to inform on the prevalence of drug resistance among TB patients, with particular focus on MDR-TB among both new and previously treated TB patients. Accordingly, the NDRS protocol was developed by National Tuberculosis Institute (NTI) and WHO for the RNTCP. 1.3 Aim and objectives Aim The aim of the survey was to find out the proportion of MDR-TB patients among new and previously treated TB patients diagnosed at RNTCP DMCs. General objective The general objective was to understand the epidemiology of DR-TB in the country to guide national policy and strategies to prevent further emergence and to control the problem. Rates of MDR/RR-TB reported under RNTCP – India’s routine surveillance data Among new TB patients Among previously treated patients 2007–2012 (n = 144 326) NA 19% 2013–2015 (n = 779 300) 5% 11% 2016 (n = 580 438) 4% 9%
  • 16. 6 Specific objectives Primary objectives  To determine the prevalence of MDR-TB among newly diagnosed sputum smear- positive TB patients;  To determine the prevalence of MDR-TB among previously treated sputum smear-positive TB patients. Secondary objectives  To determine the prevalence of second line anti-TB drug resistance in Mycobacterium tuberculosis (M. tuberculosis) strains with confirmed resistance to isoniazid and rifampicin;  To describe drug resistance patterns of M. tuberculosis strains collected from newly diagnosed sputum smear-positive TB patients;  To describe drug resistance patterns of M. tuberculosis strains collected from previously treated sputum smear-positive TB patients.
  • 17. 7 2. Materials and methods 2.1 Study design This was a cross-sectional study among all new smear-positive TB patients and all previously treated TB patients diagnosed in the RNTCP DMCs in India from August 2014 to July 2015. 2.2 Sample size determination In 2012, RNTCP notified 1 467 585 total TB patients, of which 629 589 were new sputum smear-positive TB patients, 317 616 were smear-negative TB patients, 234 029 were new extra-pulmonary TB patients and 284 212 were previously treated TB patients of which 106 463 were relapse cases, 16 400 were treatment failures, 64 782 were TB patients who were lost to follow up and 96 567 were other retreatment TB patients. This data was used for arriving at the sample size for the survey. The assumptions used to arrive at the sample size for new and previously treated patients to be enrolled in the survey are depicted in Table 3. Table 3: Assumptions made to calculate the sample size for new and previously treated patients to be enrolled in the survey Type of patient New Previously treated Initial estimate of prevalence 0.03 0.15 Relative precision 34% 40% Anticipated non-participation/loss rate 20% Design effect (due to cluster sampling) 2.5 Previous state level studies have shown MDR-TB proportion among new and previously treated TB patients as 3% and 15%, respectively. Using these as initial prevalence, the sample size was obtained with a 34% relative precision in new TB patients and 40% relative precision in previously treated TB patients. Based on the analysis of state level DRSs (DMCs as sampling units) the design effect (DEFF) was reasonably fixed at 2.5, also accounting for high levels of heterogeneity among the TB units (TUs). An anticipated non-participation or loss rate was assumed to be 20%. Thus, the sample size for new TB patients was derived as 3223 with a relative precision of 34%, i.e. (3% ± 1%) and a DEFF of 2.5 (with 20% loss included). For previously treated TB
  • 18. 8 patients with the proportion of MDR-TB at 15%, 40% relative precision, i.e. 17% ± 7% (10– 24% in previously treated overall) and DEFF of 2.5, the sample size was derived as 1991. More number of TUs would have be better for analytical purposes but may not have been practical. The fewer the number of respondents in each cluster, the lower the clustering effect, which would increase sample variance, thus effectively reducing the estimating power. Balancing both these factors, 120 TUs were chosen to account for analytic precision and logistic implementation. As the programme was under the process of further decentralization of TUs during the survey period, all the new TUs that fell under the original 120 TU clusters identified at baseline continued to contribute to the study. Sampling strategy The sampling strategy in this survey was a single-stage, weighted cluster sampling method, in which clusters were selected with probability proportional to size, with each cluster contributing a fixed number of new and previously treated TB patients. The cluster sampling methodology is appropriate for India because of the logistical challenges and laboratory capacity needed to cover all of the approximately over 14 000 DMCs in the country and around 1.5 million TB patients notified each year. The primary sampling unit in the survey was the RNTCP-defined TU and survey participants were recruited from all DMCs in the selected TUs. Each TU represented a cluster. The proportion of urban TUs in the selection was 24%. The following methodology was used to select the TU clusters. A list of all TUs in the country with the respective numbers of new sputum smear-positive TB patients, and previously treated TB patients registered in the first quarter (January–March) of 2012 was compiled. This data was annualized to calculate the estimated cumulative number of total TB patients. TUs were selected using a weighted-cluster sample technique based on new sputum smear- positive TB patients. Once TUs were selected, all DMCs in the selected TU would contribute until the enrolment of cumulative number of expected patients reached the required sample size. A total of 44 consecutive TB patients diagnosed at the DMCs from each selected TU were recruited to include 27 new TB patients and 17 previously treated TB patients per TU. Based on this, the total new and previously treated TB patients were rounded off to 3280 and 2040. Those patients who met the inclusion criteria but could not be included in the survey for various reasons were replaced by consecutive patients diagnosed in the DMCs of the same TU according to the sampling procedure described.
  • 19. 9 Inclusion criteria a) Newly diagnosed sputum smear-positive pulmonary TB patients with no history of prior treatment for TB, or a history of anti-TB treatment for less than 30 days. Enrolled patients should not have been initiated in a course of anti-TB treatment. b) Diagnosed patients with sputum smear-positive pulmonary TB with a history of previous TB episode with more than 30 days of anti-TB treatment. This may include relapses, treatment after default, treatment after failure, or other patients who have claimed to have anti-TB treatment for more than 30 days. Enrolled patients should not have been initiated in a course of anti-TB treatment for the current episode. Exclusion criteria a) Patients with sputum smear-negative pulmonary TB b) Patients with exclusively extra pulmonary TB c) Patients diagnosed at a correctional facility (i.e., jails, prisons, asylums) d) Persons unwilling or unable to give informed consent. There were no age restrictions, provided the patient fulfilled the above criteria. 2.3 Definitions Anti-TB drug resistance among new TB patients: Newly diagnosed sputum smear-positive pulmonary TB patients without a history of prior treatment for TB, or a history of treatment for less than 30 days. Enrolled patients should not have been initiated in a course of anti-TB treatment for the current episode. Anti-TB drug resistance among previously treated TB patients: Diagnosed patients with sputum smear-positive pulmonary TB with a history of prior anti-TB therapy. This may include relapse, treatment after default and treatment after failure, or other patients who have claimed to have anti-TB treatment for greater than 30 days. Enrolled patients should not have been initiated in a course of anti-TB treatment for the current episode. Multidrug resistant TB (MDR-TB): Patients with sputum smear-positive pulmonary TB with at least one M. Tuberculosis isolate with demonstrated resistance to at least isoniazid and rifampicin (with or without other first-line anti-TB drugs). Extensively drug resistant TB (XDR-TB): Patients with sputum smear-positive pulmonary TB with at least one M. Tuberculosis isolate with demonstrated resistance to isoniazid, rifampicin, at least one fluoroquinolone (ofloxacin, levofloxacin or moxifloxacin), and at least one injectable second line drug (amikacin, capreomycin or kanamycin).
  • 20. 10 2.4 Training and data collection The data collection formats included the clinical information form (CIF) and the diary of senior TB laboratory supervisors (STLS) for referral. A detailed CIF was designed for collecting data on socio-demography, occupation, income, symptoms, duration of illness, history of previous treatment, source of treatment, etc. The CIF was administered by the medical officer at the TU level along with which an informed consent for participation in the survey was also obtained from eligible patients. Bar codes were applied to specimens, sputum containers, CIF and NDRS registers for automated aligning of all survey related data collection of individual patients from all the sites of survey. A training video in English and local vernacular languages was developed for assisting the state level trainers trained at a series of national training of trainers to provide cascade training in the participating states, which gave a detailed account of all the survey procedures for data collection. In addition, dedicated in-house software was developed by NTI for real time data entry and validation. 2.5 Field activities Consecutive sputum smear-positive TB patients diagnosed at each DMC of the selected TUs were recruited according to the sampling methodology based on categorization (new or previously treated). The senior treatment supervisor (STS) or STLS coordinated among the DMCs of the respective TUs to ensure that patients were enrolled in chronological order for the study. On identification of an eligible patient, he/she was given detailed information about the survey and informed consent was obtained from each patient. Two additional specimens were collected from the patient in falcon tubes (specimen C and D) and these were transported in a bio-safe container under cool chain to NTI along with CIF. CIF was filled in by the medical officer of the DMC and cross-checked by the STS or STLS to reconfirm the categorization. CIFs of 10% of enrolled patients were re-validated by district-level staff and another 10% by the RNTCP–WHO consultant as part of the data quality assurance procedure. Recruitment continued until the numbers of patients in each category were completed. Provider-initiated HIV counselling and testing was offered to all patients as per RNTCP guidelines. The target transit time for receiving the specimens at NTI was fixed not to exceed 72 h; however, there was no rejection clause if received later than the target time. Attention was paid to transport logistics in order to minimize transportation time, prevent leakage and specimen contamination. Specimens were packed and transported as per RNTCP guidelines. Only fresh sputum specimens were transported and processed.
  • 21. 11 For patients eligible to screen for MDR-TB, two more specimens (E and F) were also collected for rapid molecular drug resistance testing as per the PMDT guidelines for routine care and MDR/RR-TB patients detected were initiated on an appropriate DR-TB regimen. DST results of the specimens processed under the NDRS were communicated by NTI to the respective district and DR-TB centre for appropriate treatment initiation or modification. 2.6 Laboratory procedures All specimens were handled in a negative-pressure environment as per the international standards for biosafety and infection control for M. tuberculosis. Two sputum specimens from each study patient were decontaminated using N-acetyl-L-cysteine–sodium citrate– sodium-hydroxide (NALC-NaOH) procedure. Microscopy using auramine-O-phenol of the concentrated deposit smear was performed and inoculated onto 7 ml MGIT tubes as per the MGIT 960 System Manual (4) and RNTCP Laboratory manual (5). Back up cultures for both specimens were maintained on LJ medium. One specimen was inoculated per tube. Tubes identified as positive by the MGIT system were further identified as M. tuberculosis-complex by using immune-chromatographic tests. DST was performed on only one positive-culture after identification as M. tuberculosis using the modified proportion sensitivity method for liquid culture system taking standard critical concentrations for isoniazid (0.1μg), rifampicin (1.0μg), streptomycin (1.0μg), ethambutol (5.0μg) and pyrazinamide (100µg) (as per the MGIT manual). For second line drugs, the drugs and concentrations as per the standard critical concentrations, i.e. kanamycin (2.5μg), amikacin (1.0μg), capreomycin (2.5μg), ofloxacin (2.0μg), levofloxacin (1.5μg), moxifloxacin (0.5µg), PAS (2.0µg) and ethionamide (5.0µg) were used (6). 2.7 Quality assurance Laboratory quality assurance (QA) (internal and external) All laboratory procedures adhered to the internal quality control (IQC) procedures as per RNTCP laboratory manual, and in accordance with international standards times (7). All data relating to the survey and records pertaining to IQC were maintained in separate registers – primary culture, identification and drug susceptibility testing, and IQC. NTI participates in the regular annual proficiency panel exercise conducted by the Antwerp WHO Coordinating Supranational Reference Laboratory (SRL). In addition, 10% of all isolates were retested at NIRT (formerly TRC), also a WHO coordinating SRL for recording reproducibility. The results of the annual proficiency testing with Antwerp were 100% for all tested first- and second line drugs. The agreement for the drugs tested in the DRS as part of reproducibility was also complete.
  • 22. 12 2.8 Data management NDRS – Laboratory Information Management System (NDRS-LIMS) With the historical experience with the manual systems used in past subnational DRS surveys in India, NDRS was expected to offer several challenges in terms of logistics, training, implementation, data management and analysis. Further, the task of monitoring a survey of this magnitude for needful interventions and course corrections from NTI and keeping the central, state and WHO monitoring committees abreast with the progress on the field with periodic reports meant that the data collection and its reflection onto reports had to be as real time as possible. Hence, a customized web-based application was designed, developed and hosted at NTI to cater to both the data collection and real time interaction with the 120 TUs for entering the external quality assessment (EQA) results and also to facilitate the survey monitoring by Central TB Division (CTD) and WHO. A state level survey monitoring committee was established in every state and was also provided individual login to access relevant information for real time monitoring of the survey. Apart from this, a customised survey specific laboratory information management system was also developed and hosted to facilitate a work flow integrated data capture mechanism. This ensured that real time reporting was available for necessary interventions by the data monitoring committee at NTI and in the states. Use of innovative tools like barcodes and optical mark recognition (OMR) sheets for result capture ensured an error-free and efficient data management process. The applications were developed using open source software MySQL database and PHP programming language. The hosting, periodic backup, data security measures commensurate with the standards were deployed. Customised unique specimen enrolment registers for each of the 120 TUs were designed with unique barcodes for 5280 patients. The date and time of specimen collection were recorded on these stickers and were affixed to the falcon specimen tubes before dispatch to NTI. 10 560 sputum smear examinations, culture examinations by both liquid and solid media and DSTs for all positive cultures had to be undertaken. In addition, Xpert MTB/RIF (GeneXpert) testing for paediatric patients was undertaken. It was essential to design a data management solution that was not only efficient, but also assisted the microbiologist to track the survey progress in terms of specimens received, specimens whose result was declared and specimens under process. Hence, a robust laboratory information management system was designed to facilitate the work process flow. All the stages of laboratory activities right from the specimen registration, specimen result declaration by lab technician and result verification by the microbiologist were captured in real time by a LAN based application. This brought in a decentralised yet effective mechanism of data
  • 23. 13 collection from the respective laboratory work benches, giving the supervisors an overview of the operations in real time. Also, pre-printed lab stationary was deployed. Only specimen and test specific result sheets were dynamically generated at the time of specimen registration with the unique barcodes printed. Thus, human errors in declaration of results to the wrong specimens were avoided as the process started by scanning of the barcodes. Also, the results were declared on optical mark recognition (OMR) sheets which were subsequently scanned and re-checked for any mismatch. These processes ensured a high degree of quality and accuracy in declaration of the laboratory results. Multilingual video e-tutors on the standard operating procedures were prepared and used for training and as ready reference for all the survey personnel using the web portal. Data analysis The data was analysed.0 and Stata ver 12 statistical packages. To ensure accuracy, double-data entry using SPSS ver 17was employed. Periodic data verification and validation exercises was conducted to ensure data accuracy To calculate the prevalence of anti-tuberculosis drug resistance, the denominator was taken to be the number of patients with valid drug susceptibility results. However, it is also important to report the number of results missing as a result, for example, of contamination, or negative cultures. A table comparing the number of patients enrolled from each diagnostic centre with the expected number of expected based on the sampling method was prepared. These were used to monitor enrolment and track specimens. A table describing the proportion of patients with resistance to individual TB drugs, and to different combinations of TB drugs, among new and previously treated patients was prepared. Proportion in age, sex, HIV status, type of re-treatment, source of previous treatment was stratified by categories of resistance. Data was stored in the dedicated system with password protection and only accessible to authorized personnel. Backup data was also stored in a separate site and server for use in case of any fault in the primary PC. Ethical issues and approval Approval of the Institutional Ethics Committee of NTI was obtained. Informed consent was obtained from all patients enrolled for the study. The DST results of all patients were
  • 24. 14 communicated to the respective health facilities for standard of TB care as per national guidelines. 2.9 Limitations The study did not include patients managed in the private sector who do not come in contact with the public health sector during the course of their disease, as getting an appropriate specimen from such patients was beyond the scope of the study. The survey was powered only for national prevalence of MDR-TB and not for state level prevalence.
  • 25. 15 3 Results, discussion and conclusion 3.1 Survey quality The survey commenced in July 2014 and 95% of the enrolments were completed by July 2015. However, the rest of the 5% took longer and were completed only by May 2016. This longer intake period was significantly contributed to by paucity of previously treated TB patients diagnosed in certain DMCs, though they had such patients during the period of sample size determination period in 2012. After the initial conduct of three rounds of training of trainers, the survey commenced as per the agreed staggered timeline, with TUs which required 12 months or more starting to contribute to survey intake and those that could contribute within 15–30 days being at the tail end of the survey period. However, during the survey, intake was initially slow due to various reasons including some logistic issues contributing to delay in intake. This was compensated during the last quarter of the survey period (Fig. 2). Fig. 2: Sample registration during the survey period PT – Previously treated Patients were enrolled from 120 TUs across the country. Of the 572 total DMCs within these 120 TUs, 530 DMCs participated in screening of patients to identify those eligible, while 524 (91.61%) DMCs contributed to survey samples. Two specimens, A and B, were collected for routine management as per standard of care articulated in the RNTCP. After obtaining an informed consent, eligible patients were requested to provide two additional specimens (C and D) each from 5280 eligible patients. These were collected and transported to NTI Bangalore along with the completely filled CIFs, barcoded as per survey protocol. The specimens were from 3240 new TB patients and 0 200 400 600 800 1000 1200 1400 Jul-14 Sep-14 Nov-14 Jan-15 Mar-15 May-15 Jul-15 Sep-15 Nov-15 Jan-16 Mar-16 May-16 All New PT 95%
  • 26. 16 2040 patients previously treated for TB. A total of 212 specimens were rejected due to various reasons and additional patients were enrolled as replacement. The quality of both specimens was good for 98% of those collected with a minimal percentage of leakage or less than 2 ml volume observed in 1.0% each as shown in Table 4. Table 4: Specimen quality Specimen quality Specimen C Specimen D Good 5140 (97.35%) 5164 (97.80%) Leaked 57 (1.08%) 54 (1.02%) Volume <2 ml 83 (1.57%) 62 (1.12%) Total 5280 5280 Culture positivity of 93.9% was achieved in the liquid culture system with additional recovery of 2.2–2.5% from Löwenstein-Jensen (LJ) media backup, which further improved the culture recovery rates. DST was performed on culture growth from specimens of 3064 (94.57%) patients out of 3240 new TB patients and 1893 (92.79%) out of 2040 previously treated TB patients as shown in Table 5. Table 5: Status of DST availability among enrolled patients New TB patients Previously treated patients All patients Number enrolled 3240 2040 5280 DST Available 3064 (94.57%) 1893 (92.79%) 4957 (93.88%) 3.2 Participant profile Age and gender distribution is shown in Tables 6 and 7. Seventy-two percent (72.01%) of the survey participants were males and 27.99% were females. Children in the 0–14 years age group contributed to 1.7% of the survey population. Though males were predominant in all age groups in terms of absolute numbers except in the 0–14 years age group, more than 60% of females were aged less than 34 years. The age and gender distribution of survey participants were similar to the distribution of smear positive TB patients registered in RNTCP in 2015.
  • 27. 17 Table 6: Gender distribution and type of patients among participants Gender New TB patients (%) Previously treated patients (%) All patients (%) Female 1,013 (31.37%) 465 (22.79%) 1478 (27.99%) Male 2227 (68.73%) 1575 (77.97%) 3802 (72.01%) Total 3240 (100%) 2040 (100%) 5280 (100%) Table 7: Age distribution and type of patients among participants 3.3 MDR-TB/XDR-TB among new and previously treated TB patients Among the 4958 TB patients with DST results, 28% had resistance to one or the other anti- TB drug, while 6.19% had MDR-TB. Among the 307 MDR-TB patients, 11 (3.58%) and 67 (21.82%) patients had additional resistance to any drug from second line injectable class and any drug from fluoroquinolone class, respectively; i.e. pre-XDR-TB. Thus, among the 78 preXDR-TB patients, most of the patients (67 [86%]) had additional fluoroquinolone resistance. XDR-TB among MDR-TB patients was 1.3%. (Table 8). Age group (years) Female (%) Male (%) Total (%) (0–14) 69 (4.70%) 21 (0.60%) 90 (1.7%) (15–24) 462 (31.30%) 636 (16.70%) 1098 (20.80%) (25–34) 377(25.50%) 757 (19.90%) 1134 (21.50%) (35–44) 211(14.30%) 752(19.80%) 963(18.20%) (45–54) 155(10.50%) 752 (19.80%) 907(17.20%) (55–64) 138(9.30%) 541 (14.20%) 679 (12.90%) 65+ 66(4.50%) 343 (9.00%) 409 (7.70%)
  • 28. 18 Table 8: MDR-TB/XDR-TB among new and previously treated TB patients New TB patients (95% CI) Previously treated patients (95% CI) All patients (95% CI) DST results 3065 1893 4958 Susceptible 2374 (77.46%) (75.93–78.92%) 1196 (63.18%) (60.96–65.36%) 3570 (72.01%) (70.73–73.25%) Any DR 691 (22.54%) (21.10–24.10%) 697 (36.82%) (34.64–39.04%) 1388 (28.00%) (26.77–29.29%) MDR 87 (2.84%) (2.28–3.49%) 220 (11.62%) (10.21–13.15%) 307 (6.19%) (5.54–6.90%) MDR + any SLI 6 (6.90%) (2.57–14.41%) 5 (2.27%) (0.74–5.22%) 11 (3.58%) (1.80–6.32%) MDR + any FQ 21 (24.14%) (15.60–34.50%) 46 (20.91%) (15.73–26.89%) 67 (21.82%) (17.33–26.87%) XDR 2 (2.30%) (0.28–8.06%) 2 (0.91%) (0.11–3.25%) 4 (1.30%) (0.36–3.30%) Among the 3065 new TB patients subjected to DST for 13 drugs, 2374 (77.46%) were susceptible to all drugs tested, while 691 (22.54%) showed resistance to any drug. MDR-TB was detected in 87 (2.84%) of the new TB patients tested as shown in Table 8. Mono resistance to rifampicin was not observed among new TB patients, thereby indicating that rifampicin resistance was always accompanied by isoniazid resistance. 3.4 Individual drug resistance pattern among new and previously treated TB patients Among the 1893 previously treated TB patients subjected to DST, 1196 (63.18%) were susceptible to all drugs while 697 (36.82%) showed resistance to any drug. MDR-TB was detected in 220 (11.62%) patients (Table 9). Mono resistance to rifampicin was observed in one patient (0.05%) among the previously treated TB patients.
  • 29. 19 Table 9: Individual drug resistance patterns Drugs New patients Previously treated patients % any resistance (95% CI) % mono resistance (95% CI) % any resistance (95% CI) % mono resistance (95% CI) Streptomycin 6.88 (6.01–7.84) 2.22 (1.73–2.81) 13.26 (11.76–14.87) 2.48 (1.83–3.29) Isoniazid 11.06 (9.97–12.22) 3.85 (3.20–4.60) 25.09 (23.15–27.11) 7.61 (6.45–8.89) Rifampicin 2.84 (2.28–3.49) 0 (0.0) 11.67 (10.26–13.21) 0.05 (0.001–0.29) Ethambutol 2.28 (1.78–2.88) 0.23 (0.092–0.47) 7.03 (5.92–8.27) 0.21 (0.06–0.54) Pyrazinamide 6.95 (6.07–7.91) 4.11 (3.44–4.88) 8.77 (7.53–10.13) 4.07 (3.22–5.06) Kanamycin 1.01 (0.69–1.43) 0.03 (0.0–0.18) 1.01 (0.61–1.56) 0 (0.0) Amikacin 0.98 (0.66–1.39) 0.07 (0.01–0.24) 1.01 (0.61–1.56) 0.05 (0.001–0.29) Capreomycin 1.04 (0.72–1.47) 0.03 (0.02–0.18) 0.85 (0.48–1.37) 0 (0.0) Ofloxacin 3.72 (3.08–4.45) 0.59 (0.35–0.93) 6.29 (5.23–7.48) 0.95 (0.56–1.50) Levofloxacin 2.71 (2.16–3.35) 0.1 (0.02–0.29) 3.75 (2.94–4.71) 0 (0.0) Moxifloxacin 2.58 (2.04–3.20) 0.07 (0.01–0.24) 4.01 (3.18–4.99) 0 (0.0) Para‐amino salicylic sodium 2.32 (1.81–2.91) 0.33 (0.16–0.60) 2.38 (1.74–3.17) 0.42 (0.18–0.83) Ethionamide 2.54 (2.02–3.17) 0.33 (0.16–0.60) 3.06 (2.33–3.94) 0.26 (0.09–0.62)
  • 30. 20 Drug resistance patterns of M. tuberculosis strains collected from newly diagnosed sputum smear-positive TB patients Resistance patterns to individual first-line drugs tested indicated highest resistance to isoniazid (any 11.06%, mono 3.85%) followed by resistance for pyrazinamide (any 6.95%, mono 4.11%), streptomycin (any 6.88%, mono 2.22%) and ethambutol (any 2.28%, mono 0.23%) as shown in Table 9. Resistance patterns to individual second line drugs tested indicated highest resistance to ofloxacin (any 3.72%, mono 0.59%) followed by resistance for levofloxacin (any 2.71%, mono 0.1%), moxifloxacin (any 2.58%, mono 0.07%), ethionamide (any 2.54%, mono 0.33%), para-amino salicylic acid sodium (any 2.32%, mono 0.33%), capreomycin (any 1.04%, mono 0.03%), kanamycin (any 1.01%, mono 0.03%) and amikacin (any 0.98%, mono 0.33%) as shown in Table 9. Drug resistance patterns of M. tuberculosis strains collected from previously treated sputum smear-positive TB patients Resistance patterns to individual first-line drugs tested indicated highest resistance to isoniazid (any 25.09%, mono 7.61%) followed by resistance for streptomycin (any 13.26%, mono 2.48%), pyrazinamide (any 8.77%, mono 4.07%), and ethambutol (any 7.03%, mono 0.21%) as shown in Table 9. Resistance patterns to individual second line drugs tested indicated highest resistance to ofloxacin (any 6.29%, mono 0.95%) followed by resistance for moxifloxacin (any 4.01%, mono 0.0%), levofloxacin (any 3.75%, mono 0.0%), ethionamide (any 3.06%, mono 0.26%), para-amino salicylic acid sodium (any 2.38%, mono 0.42%), amikacin (any 1.01%, mono 0.05%), kanamycin (any 1.01%, mono 0.0%) and capreomycin (any 0.85%, mono 0.0%) as shown in Table 9. 3.5 Additional first-line anti-TB drug resistance among confirmed MDR-TB patients Among the 87 new TB patients with MDR-TB, any resistance to other first-line drugs was also observed to be high for streptomycin 70.1% (CI 59.35-79.46%), followed by ethambutol 45.98% (CI 35.23–57.0%), and the least for pyrazinamide 31.03% (21.55–41.86%). Among the 220 previously treated TB patients with MDR-TB, any resistance to other first- line drugs was observed to be highest for streptomycin 59.09% (CI 52.28–65.65%), followed by ethambutol 46.36% (CI 39.64–53.19%) and the least for pyrazinamide 20.45% (CI 15.33– 26.40%).
  • 31. 21 3.6 Additional second line anti-TB drug resistance among confirmed MDR- TB patients Amongst the 87 new TB patients with MDR-TB, 21 (24.14%) had additional resistance to any fluoroquinolone and 6 (6.90%) to any second line injectable drugs. XDR-TB was observed in 2 (2.30%) patients among MDR-TB patients (Table 8). Further, any resistance to other second line drugs was observed to be highest for ofloxacin 24.14% (CI 15.6–34.5%), followed by moxifloxacin 18.39% (CI 10.89–28.14%), levofloxacin 17.24% (CI 9.98–26.84%), ethionamide and PAS 11.49% (CI 5.65–20.12%) each, amikacin and capreomycin 8.05% (CI 3.3–15.88%) each and the least for kanamycin 4.6% (CI 1.27–11.36%). Among the previously treated TB patients with MDR-TB, 46 (20.91%) had additional resistance to any fluoroquinolone and 5 (2.27%) to any second line injectable drugs. XDR-TB was observed in 2 (0.91%) patients (Table 8). Further, any resistance to other second line drugs was observed to be highest for ofloxacin 21.36% (CI 16.14–27.38%), followed by moxifloxacin 15.45% (CI 10.95–20.92%), levofloxacin 14.09% (CI 9.78–19.40%), ethionamide 7.27% (CI 4.21–11.55%), PAS 4.09% (CI 1.89–7.62%), kanamycin and amikacin 2.27% (CI 0.74–5.22%) each and the least for capreomycin 1.81% (CI 0.49–4.59%). 3.7 DR-TB rates among states Sample size for the survey was calculated for obtaining national level estimates only and State level inferences cannot be drawn directly from the survey. However, resistance to any drug as well as distribution of MDR among the States that participated suggests areas for focus action. State-wise drug resistance rates are given in Table 10 using the numbers collected from each state that provided specimens for the survey. A state level analysis of drug resistance indicates that DR-TB is prevalent in all states, albeit with wide variations ranging from 18.42% in Himachal Pradesh to 36.84% in Jammu & Kashmir. In addition, this is an indication that screening of drug resistance has to be expanded to offer universal DST including expanded DST as envisaged in the updated PMDT guidelines. The second and most important activity is to strengthen drug resistance surveillance under the programme with inclusion of laboratories in the private sector as well. The state levels rates also give us the opportunity to plan and execute intervention prioritizing, based on the drug resistance trends observed.
  • 32. 22 Table 10: DR-TB rates among different states in India State New TB patients Previously treated TB patients TotalDST result MDR %MDR DR(other thanMDR) %DR(other thanMDR) TotalDST result MDR %MDR DR(other thanMDR) %DR(other thanMDR) Andhra Pradesh 183 1 0.55 40 21.86 114 9 7.89 25 21.93 Assam 79 2 2.53 20 25.32 48 2 4.17 16 33.33 Bihar 177 8 4.52 32 18.08 109 16 14.68 22 20.18 Chhattisgarh 47 2 4.26 9 19.15 33 2 6.06 11 33.33 Delhi 80 1 1.25 17 21.25 46 4 8.70 13 28.26 Gujarat 183 3 1.64 26 14.21 113 6 5.31 17 15.04 Haryana 53 0 0.00 6 11.32 31 4 12.90 11 35.48 Himachal Pradesh 23 1 4.35 2 8.70 15 0 0.00 4 26.67 Jammu & Kashmir 26 0 0.00 7 26.92 12 0 0.00 7 58.33 Jharkhand 103 2 1.94 13 12.62 62 7 11.29 13 20.97 Karnataka 128 0 0.00 37 28.91 81 1 1.23 24 29.63 Kerala 53 1 1.89 9 16.98 27 3 11.11 5 18.52 Madhya Pradesh 142 3 2.11 25 17.61 88 9 10.23 28 31.82 Maharashtra 259 20 7.72 50 19.31 161 19 11.80 41 25.47 Meghalaya 24 0 0.00 6 25.00 15 2 13.33 1 6.67 Nagaland 26 1 3.85 4 15.38 16 2 12.50 6 37.50 Orissa 106 0 0.00 27 25.47 66 7 10.61 17 25.76 Punjab 78 1 1.28 10 12.82 46 2 4.35 15 32.61 Rajasthan 179 5 2.79 34 18.99 116 15 12.93 33 28.45 Sikkim 25 1 4.00 6 24.00 17 3 17.65 2 11.76 Tamil Nadu 138 4 2.90 21 15.22 90 7 7.78 24 26.67 Telangana 53 0 0.00 16 30.19 33 5 15.15 7 21.21 Uttar Pradesh 640 29 4.53 133 20.78 399 79 19.80 96 24.06 Uttarakhand 54 1 1.85 12 22.22 30 6 20.00 7 23.33 West Bengal 205 1 0.49 42 20.49 125 10 8.00 32 25.60 Total 3064 87 2.84 604 19.71 1893 220 11.62 477 25.20
  • 33. 23 3.8 Conclusions Key findings  Among all TB patients tested, MDR-TB rate was 6.19% with 2.84% among new and 11.60% among previously treated TB patients.  Any isoniazid resistance among new and previously treated TB patients was 11.06% and 25.09%, respectively.  Any drug resistance among new TB patients was 22.54%, with 36.82% among previously treated TB patients and 28.02% among all patients.  There was negligible rifampicin mono-resistance in the survey and isoniazid resistance was invariably associated with rifampicin resistance. Any pyrazinamide resistance was 6.95% and 8.77% among new and previously treated TB patients, respectively.  Among MDR-TB patients, additional resistance to any fluoroquinolone was 21% and any second line drug resistance was 3.84%.  Among MDR-TB patients, XDR-TB rate was 1.3%.  There were wide variations in the state-wise levels of drug resistance (Table 10), highlighting that national level estimates tends to mask the local and focal epidemics that need to be addressed with specific interventions. Key steps going forward The key next steps are:  Setting up and strengthening drug resistance surveillance including using state of art next generation sequencing. This will provide the programme with the trends of drug resistance, transmission patterns and mapping of hot spots in different states for better understanding of molecular epidemiology for TB surveillance.  Rapidly scaling up universal DST and appropriate DST guided treatment.  Strengthening epidemiologic intelligence for specific interventions based on local epidemiological profile.
  • 34. 24 References 1. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016 (www.who.int/tb/publications/global_report, accessed 19 December 2017). 2. World Lung Conference 2010 – Association of poor culture conversion with fluoroquinolone resistance in Gujarat, Western India..R.N. Solanki, P V Dave, T V Bhalodia, S Chadha, F Wares, N Selvakumar, L S Chauhan, P Dewan 3. Surveillance of drug-resistant tuberculosis in the state of Gujarat, India. Ramachandran R, Nalini S, Chandrasekar V, Dave PV, Sanghvi AS, Wares F, et al. Int J Tuberc Lung Dis. 2009;13(9):1154–60. 4. Siddiqui SH, Rüsch-Gerdes S. MGITTM Procedure Manual. Geneva: Foundation for Innovative New Diagnostics; 2006. 5. Revised National TB Control Programme Training Manual for Mycobacterium tuberculosis Culture & Drug susceptibility testing. https://tbcindia.gov.in/showfile.php?lid=2991 6. Policy guidance on drug-susceptibility testing (DST) of second-line anti-tuberculosis drugs. Geneva: World Health Organization; 2008 (WHO/HTM/TB/2008.392, accessed 19 December 2017). 7. Guidelines for surveillance of drug resistance in tuberculosis - 5th edition. Geneva: World Health Organization; 2015 (WHO/HTM/TB/2015.13, accessed 19 December 2017).